Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Ourania S. Kotsiou
 + 2718 word(s) 2718 2021-02-20 03:38:07 |
2 format correct
Vivi Li
 + 1 word(s) 2719 2021-02-26 04:10:36 | |
3 format correct
Vivi Li
 + 1 word(s) 2719 2021-02-26 04:10:59 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Kotsiou, O.S. Calprotectin in Lung Diseases. Encyclopedia. Available online: https://encyclopedia.pub/entry/7602 (accessed on 27 July 2024).
Kotsiou OS. Calprotectin in Lung Diseases. Encyclopedia. Available at: https://encyclopedia.pub/entry/7602. Accessed July 27, 2024.
Kotsiou, Ourania S.. "Calprotectin in Lung Diseases" Encyclopedia, https://encyclopedia.pub/entry/7602 (accessed July 27, 2024).
Kotsiou, O.S. (2021, February 25). Calprotectin in Lung Diseases. In Encyclopedia. https://encyclopedia.pub/entry/7602
Kotsiou, Ourania S.. "Calprotectin in Lung Diseases." Encyclopedia. Web. 25 February, 2021.
Calprotectin in Lung Diseases
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms22041706

Calprotectin (CLP) is a heterodimer formed by two S-100 calcium-binding cytosolic proteins, S100A8 and S100A9. It is a multifunctional protein expressed mainly by neutrophils and released extracellularly by activated or damaged cells mediating a broad range of physiological and pathological responses. It has been more than 20 years since the implication of S100A8/A9 in the inflammatory process was shown; however, the evaluation of its role in the pathogenesis of respiratory diseases or its usefulness as a biomarker for the appropriate diagnosis and prognosis of lung diseases have only gained attention in recent years. This entry aimed to provide current knowledge regarding the potential role of CLP in the pathophysiology of lung diseases and describe how this knowledge is, up until now, translated into daily clinical practice. CLP is involved in numerous cellular processes in lung health and disease. In addition to its anti-microbial functions, CLP also serves as a molecule with pro- and anti-tumor properties related to cell survival and growth, angiogenesis, DNA damage response, and the remodeling of the extracellular matrix.

biomarker calgranulin calprotectin lung S100A8/A9

1. Introduction

Calprotectin (CLP) is a heterodimeric complex formed by two binding proteins of the calcium ion, which belong to the S-100 protein family, S100A8 and S100A9, having both anti-inflammatory and anti-bacterial properties. The first applied name to CLP was major leukocyte protein L1 or 27E10 [1][2][3]. It was later recognized as the combination of S100A8 and S100A9, while various synonyms have also been adopted, such as myeloid-related proteins-8 and -9 (MRP-8 and MRP-9), calgranulin A and B, or migration inhibitory factor-related protein of 8 and 14 kDa (MRP-8 and MRP-14), respectively [1][2][3].

CLP represents almost two-thirds of the soluble cytosolic protein content of neutrophils. CLP may also be detected at various levels in monocytes, macrophages, epithelial cells, and platelets [4][5]. It is expressed as an anti-bacterial agent, mainly but not exclusively by neutrophils, when activated [3]. Upon cell activation or death, CLP is released extracellularly, acts as an alarmin, or damage-associated molecular pattern (DAMP). It serves as a stimulatory ligand for the innate cell-surface receptors such as receptor for advanced glycation end products (RAGE) and Toll-like receptor 4 (TLR4) [4][5]. However, there are data demonstrating that physiological levels of S100A9 homodimers can trigger an inflammatory response in vivo despite the capacity of RAGE and TLR4 blockade to inhibit responses in vitro [6]. CLP inhibits the oxidative metabolism of polymorphonuclear neutrophils in vitro, an effect that can be potentiated by the controlled activation of the protease-activated receptor-2 (PAR2) [7]. In particular, the survival rate was almost doubled from 33% to 65% or 63% in mice treated with S100A8 or PAR2 activating peptide, respectively, whereas 85% of the mice were treated with both PAR2 activating peptide and S100A8 survived at a statistically significant higher rate than those treated with a single agent [7].

CLP has an important epithelial barrier function, and proper levels of the heterodimer may be needed for both immune defense and homeostasis [8][9]. CLP has microbicidal, cytotoxic functions via heavy-metal detoxification [10]. CLP plays a critical role in multiple cellular processes, including cell cycle progression, proliferation, differentiation, chemotaxis, migration in a calcium-dependent manner, and survival, as well as in redox regulation, proteins’ phosphorylation, and cytoskeletal components rearrangement [5][10][11][12]. The features that CLP possesses, such as its small size, easy diffusion between tissue and blood, and enzymatic degradation resistance, make it a sensitive marker of neutrophil activation anywhere in the body [11][12].

2. The Expression of CLP in Lung Tissue and Potential Mechanisms of Extracellular Release of Human Phagocyte CLP

It has been previously shown that S100A9 is not basally present in the healthy airway epithelial cells but is highly expressed in type II pneumocytes in alveoli [8][9][13]. However, a study found that after an Alternaria exposure, S100A9 expression was high both in the alveolar and bronchial epithelium as a response to local environmental stress [9]. Similarly, S100A8 and S100A9 protein secretion was stimulated in the secretions of human bronchial epithelial cells and primary human bronchial epithelial cells after lipopolysaccharide stimulation [14]. Intranasal administration of murine S100A9 adenovirus induced a time-dependent influx of macrophage that coexisted with increased S100A9 levels and pro-inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) [6]. Conversely, other authors found no increase of CLP in healthy human peripheral airways after local endotoxin exposure [15].

A much-debated issue is how fast CLP is released from cells in response to encounters with bacteria or PAMPs. In animals with a severe bacterial infection, CLP elevation has been described after two days [16]. Another animal study described similar findings a few hours after endotoxin challenge [15]. Activation and differentiation of alveolar monocytes into MRP-8/14-positive mature macrophages with the progress of asphyxia duration have been detected in specimens of suffocated human lungs [17]. Human data on the kinetics of CLP are scarce. Van Zoelen et al. described early changes to CLP levels in healthy volunteers after endotoxin challenge with very low endotoxin doses [18]. Lipsey et al. found that although an early phenomenon, the release of CLP might not be the first line of bacterial or endotoxin inflammatory response [19]. In earlier stages of neutrophil activation, neutrophils underwent degranulation whilst keeping the integrity of their cell membrane. In this process, they would release their granular contents, such as gelatinase, myeloperoxidase (MPO), and Oncostatin M (OSM), which have also potential roles in inflammation and infection [19].

In long alveolar asphyxia cases, a 2-fold up to a 4-fold increase of MRP-8/MRP-14 was shown compared to short asphyxia [17]. In freshly isolated monocytes during prolonged cultivation, a strong upregulation of CLP was only observed during the first 3–4 days and then declined [20]. MRP-8 (S100A8) and MRP-14 (S100A9) were expressed at defined stages of monocyte/macrophage differentiation and specifically at the stage between the resting, circulating blood monocytes and the mature tissue macrophage [20]. At the same time, while MRP-14 was expressed to varying degrees by intravascular monocytes and perivascular macrophages in acute and chronic inflammation, MRP-8 was only detected in the macrophages of chronic but not acute inflammatory tissues [20]. These data provide evidence implicating the involvement of additional triggers accelerating the recruitment of macrophages under various inflammatory conditions [20] and support that chronic inflammation is mirrored by the presence of MRP-8-positive macrophages in the tissue. Hence, it seems that the characterization of subpopulations within the alveolar macrophages may be a useful tool for discriminating inflammatory statutes and monitoring disease progression. Alongside this, it has been demonstrated an extremely high increase of MRP-8/14 levels in traumatic deaths due to extreme stress and an immediate release of catecholamines and further mediators at maximal levels within seconds [21][22][23]. Recently, distinct exercise-intensity-dependent changes in serum CLP following various types of extreme physical exertion in healthy volunteers have been reported [24].

Another major topic is how CLP is released from neutrophils or other cells where it is found, including monocytes and macrophages. Although it has been proposed that S100A8/A9 extracellular release exclusively correlates with neutrophil necrosis, or disruption of the neutrophil cell membrane, more recent data have demonstrated that CLP is secreted either via distinct mechanisms of secretion or following the activation of different signal transduction pathways from undamaged cells [25].

CLP is secreted by resting and stimulated neutrophils [26]. S100A8/A9 has been reported in granules [27], suggesting that it could be released following neutrophil degranulation [27]. Hetland et al. previously reported the release of S100A8/A9 by neutrophils stimulated with N-Formylmethionyl-leucyl-phenylalanine (fMLP), a potent inducer of degranulation [28]. Nevertheless, recent evidence suggests that degranulation is not involved in the secretion of S100A8/A9 from neutrophils [26]. Calcium mobilization induced by fMLP could activate the translocation of S100A8/A9 to the plasma membrane or cytoskeleton [29][30], which could explain the disappearance of S100A8/A9 in the cytosol reported by Hetland et al. although this translocation is not sufficient to allow its secretion. Other signals are therefore necessary to induce the secretion of calgranulins. Another possible route of secretion for calgranulins is vesicular secretion, which depends on intracellular membrane-bound intermediates that need to fuse with plasma membranes to release cargo into the extracellular space. Such mechanisms involve either secretory lysosomes, exosomes derived from multivesicular bodies, or microvesicle shedding from cell surfaces [31]. Urban et al. supported that the heterodimer CLP is released in neutrophil extracellular traps (NETs) as the major anti-microbial component [32]. According to the authors, NET formation is a mechanism that ensures the interaction between cytoplasmic CLP and extracellular microbes at high local concentrations [32]. Monocytes secrete S100A9 and S100A8/A9, but not S100A8 alone, upon stimulation with pokeweed mitogen [33]. Moreover, a non-classical and tubulin-dependent secretion mechanism was shown in monocytes activated by stress [34] and inflammatory cytokines [35]. Besides, S100A9 has been found to be actively released to the extracellular environment via DDX21–TRIF signaling from undamaged macrophages, resulting in an exaggerated lung inflammatory response and cell death during influenza infection. Activation of protein kinase C by pro-inflammatory stimuli and elevation of intracellular [Ca2+] following contact with activated endothelium, collagen, or fibronectin can also stimulate S100A8/A9 release from phagocytes [36][37][38][39].

3. CLP in Respiratory Infections

In pneumonia patients, CLP levels are elevated in BALF, lung tissue, and serum [40][41]. Moreover, calgranulins exist in the heterodimeric form in secretions of pneumonia patients in vivo [42]. Interestingly, serum CLP emerges as both a potential early marker of bacterial etiology and a predictor for five-year all-cause mortality in community-acquired pneumonia [43][44]. Messenger RNA (mRNA) sequencing from the peripheral blood of patients with pneumonia revealed that S100A9 might contribute solely to mild pneumonia [43].

CLP is a major component of neutrophils that is released upon infection or injury. It is essential for protective immunity during infection by a variety of micro-organisms through its capacity to chelate a number of first-row transition metals, including manganese Mn(II), iron Fe(II), and zinc Zn(II), withholding these essential nutrients from microbes [40][41]; thus inhibiting microbial growth [5]. The ability of CLP to affect Mn(II) availability to microbes was first recognized during studies of murine tissue abscesses infected with the Gram-positive opportunistic human pathogen Staphylococcus aureus [45] and later examined for the Gram-negative gastrointestinal pathogen Salmonella enterica serovar Typhimurium [46]. More recently, the metal competition between human CLP and bacterial metal transport machinery was evaluated, and it was found that CLP outcompetes bacterial Mn(II)-acquisition proteins under conditions of high carbonic anhydrase II, as found in the extracellular environment [47]. It is important to note that Mn, Fe, and Zn acquisition systems are viable therapeutic targets to combat multidrug-resistant microbial infections [48]. In sharp contrast to the reported host-protective role of CLP in several infections, a previous study reveals that in a model of community-acquired pneumonia, CLP is misused by Streptococcus pneumoniae, facilitating bacterial growth by attenuating Zn toxicity toward the pathogen [41].

Μost studies highlighted that CLP is strongly involved in the transepithelial migration of neutrophils and macrophages to the alveoli in streptococcal pneumonia [44][49]. CLP contributes to the host response to pneumococcal infection by increasing circulating neutrophils principally by regulating granulocyte colony-stimulating factor (G-CSF) production [49]. Mainly in pneumonia, compared to chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis, alveolar macrophages are characterized by an increased MRP-8/MRP-14 expression [50].

Staphylococcus aureus pneumonia has been associated with a substantial CLP rise in BALF and lung tissue [44]. CLP serves an unexpected protective role for the lung in staphylococcal pneumonia [44]. MRP-14 deficiency affected Staphylococcus clearance and was associated with increased cytokine levels and diminished transmigration of neutrophils into BALF at late time-points after infection, together with reduced release of nucleosomes [44].

In the case of Acinetobacter baummani pneumonia, it has been reported that CLP is detectable within six hours of infection as immune cells respond to the invading pathogen and as the bacterial burden decreases, signals from the CLP decrease [48][51]. CLP inhibits Acinetobacter baumannii growth in vitro through the chelation of Mg (II) and Zn(II). Zn limitation reverses carbapenem resistance in multidrug-resistant Acinetobacter baumannii underlining the clinical relevance of increased CLP activity [48]. Consistent with the in vitro data, imaging mass spectrometry revealed that CLP accompanies neutrophil recruitment to the lung and accumulates at foci of infection in a murine model of Acinetobacter baumannii pneumonia [48].

CLP is also a key player in protective innate immunity during Klebsiella pneumonia [41]. Moreover, elevated levels of CLP detected by ELISA have been reported in the case of Burkholderia mallei infection, another Gram-negative, bipolar, aerobic bacterium, which is complicated with skin and lung abscesses [52]. CLP has also been used as a marker of alveolar NET formation, NETosis, and neutrophilic inflammation in ventilator-associated pneumonia [53]. S100A8/A9 proteins increase during lung injury and contribute to inflammation induced by high tidal volume mechanical ventilation combined with lipopolysaccharide. Nevertheless, in the absence of lipopolysaccharide, high levels of extracellular S100A8/A9 still amplify ventilator-induced lung injury via TLR4 [54]. S100A8 was found to induce IL-10 in vivo, initiating a feedback loop that attenuates acute lung injury [55].

In children, CLP was found significantly elevated in the sputum of patients with bronchiolitis obliterans as a marker of ongoing neutrophilic inflammation [56]. Some studies provide evidence for a transient inflammation in the lung characterized by very early recruitment of neutrophils associated with high expression levels of S100A8 and S100A9 proteins in filarian infections [57]. Besides, CLP plays a critical role in regulating Leishmania infection [58]. The rapid secretion of CLP by neutrophils at the site of infection protects uninfected macrophages and favors a more efficient innate inflammatory response against Leishmania infection, revealing how CLP can subvert this pathogen’s action [58].

CLP is released during mycobacterial infection in vitro and in vivo [59] Studies revealed that serum S100A9 levels are significantly increased in tuberculosis than in other lung diseases [60], suggesting that S100A9 may be a potential diagnostic biomarker for pulmonary tuberculosis [60][61]. It has also been proposed that targeting S100A8/A9 proteins can decrease lung tissue damage without impacting protective immunity against tuberculosis [62]. Furthermore, S100A9 has been associated with tuberculosis development and can distinguish between different disease stages [63].

A major pathologic role for S100A8/A9 proteins in mediating neutrophil accumulation and inflammation associated with tuberculosis has been published. CLP-positive neutrophils were abundant in regions adjacent to the caseum, supporting the concept that granulomas have organized microenvironments that balance anti-microbial, anti-inflammatory responses to limit pathology in the lungs [62]. S100A9 has been strongly expressed in all granulomatous conditions, while S100A8 has been variably expressed. An old study shows differences in immunophenotype between non-phagocytic mononuclear phagocytes in epithelioid giant cells granulomas without necrosis due to delayed cell-mediated immune reactions and phagocytic mononuclear phagocytes in caseating granulomas [64]. Mononuclear phagocytes in granulomas of foreign body type, cat-scratch disease, and erythema nodosum strongly expressed S100A8 [65]. In contrast, S100A8 expression was weak or absent in mononuclear phagocytes of sarcoidosis and tuberculosis [65].

Regarding multiorgan tuberculosis, it has been shown that high fecal CLP levels could differentiate intestinal from pulmonary tuberculosis [55]. High fecal CLP levels in intestinal tuberculosis were associated with granulomas in intestinal biopsies [66]. Patients with combined pulmonary and intestinal tuberculosis had the highest serum CLP (6.5 mg/L) and presented more severe disease [67]. The functional impairment of interaction between Zn finger genes and interferon-stimulated genes, along with a higher expression of S100A8/A9 genes, possibly form the genomic basis of tuberculosis-associated immune reconstitution inflammatory syndrome (IRIS) in a subset of patients with human immunodeficiency virus (HIV) while on highly active antiretroviral therapy [67][68].

MRP-8/14 has also been implicated in the autophagy-mediated elimination of intracellular Mycobacterium bovis by promoting reactive oxygen species generation, which may provide a promising therapeutic target for tuberculosis and other intracellular bacterial infectious diseases [65].

During the challenging global times of coronavirus disease 2019 (COVID-19), serum CLP levels have been found to track closely with current and future COVID-19 severity and in-hospital mortality [69], be positioned as an early indicator of respiratory failure [70], and therefore immunomodulatory treatment. These observations implicate neutrophils as potential perpetuators of inflammation and respiratory compromise in COVID-19 [71]. Moreover, patients with COVID-19-associated thrombosis had significantly higher blood levels of NETs and neutrophil activation markers such as CLP compared with COVID-19 patients without thrombosis [72]. Additionally, many studies support that fecal CLP indicates intestinal inflammation in COVID-19 [73][74][75].

Overall, the existing evidence supported that CLP plays an important role in eliminating microbes via leukocyte and macrophage migration at early and late time points after infection and potentially via preventing microbial acquisition of the essentials first-row transition metals. CLP has been suggested as a diagnostic and prognostic indicator of several microbial infections in daily clinical practice, and it is timidly recognized as a promising therapeutic target.

References

  1. Goebeler, M.; Roth, J.; van den Bos, C.; Ader, G.; Sorg, C. Increase of calcium levels in epithelial cells induces translocation of calcium-binding proteins migration inhibitory factor-related protein 8 (MRP8) and MRP14 to keratin intermediate filaments. Biochem. J. 1995, 309, 419–424.
  2. Edgeworth, J.; Gorman, M.; Bennett, R.; Freemont, P.; Hogg, N. Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. J. Biol. Chem. 1991, 266, 7706–7713.
  3. Ometto, F.; Friso, L.; Astorri, D.; Botsios, C.; Raffeiner, B.; Punzi, L.; Doria, A. Calprotectin in rheumatic diseases. Exp. Biol. Med. 2016, 242, 859–873.
  4. Dale, I.; Brandtzaeg, P.; Fagerhol, M.K.; Scott, H. Distribution of a new myelomonocytic antigen (L1) in human peripheral blood leukocytes: Immunofluorescence and immunoperoxidase staining features in comparison with lysozyme and lactoferrin. Am. J. Clin. Pathol. 1985, 84, 24–34.
  5. Shabani, F.; Farasat, A.; Mahdavi, M.; Gheibi, N. Calprotectin (S100A8/S100A9): A key protein between inflammation and cancer. Inflamm. Res. 2018, 67, 801–812.
  6. Chen, B.; Miller, A.L.; Rebelatto, M.; Brewah, Y.; Rowe, D.C.; Clarke, L.; Czapiga, M.; Rosenthal, K.; Imamichi, T.; Chen, Y.; et al. S100A9 induced in-flammatory responses are mediated by distinct damage associated molecular patterns (DAMP) receptors in vitro and in vivo. PLoS ONE 2015, 10, e0115828.
  7. Sun, Y.; Lu, Y.; Engeland, C.G.; Gordon, S.C.; Sroussi, H. The anti-oxidative, anti-inflammatory, and protective effect of S100A8 in endotoxemic mice. Mol. Immunol. 2013, 53, 443–449.
  8. Manni, M.L.; Alcorn, J.F. Calprotectin-g the lung during type 2 allergic airway inflammation. Am. J. Respir. Cell Mol. Biol. 2019, 61, 405–407.
  9. Palmer, L.D.; Maloney, K.N.; Boyd, K.L.; Goleniewska, A.K.; Toki, S.; Maxwell, C.N.; Chazin, W.J.; Peebles, R.S., Jr.; Newcomb, D.C.; Skaar, E.P. The innate immune protein S100A9 protects from T-helper cell type 2-mediated allergic airway inflam-mation. Am. J. Respir. Cell Mol. Biol. 2019, 61, 459–468.
  10. Vogl, T.J.; Tenbrock, K.; Ludwig, S.; Leukert, N.; Ehrhardt, C.; Van Zoelen, M.A.D.; Nacken, W.; Foell, D.; Van Der Poll, T.; Sorg, C.; et al. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat. Med. 2007, 13, 1042–1049.
  11. Røseth, A.G.; Fagerhol, M.K.; Aadland, E.; Schjønsby, H. Assessment of the neutrophil dominating protein calprotectin in feces: A methodologic study. Scand. J. Gastroenterol. 1992, 27, 793–798.
  12. Berntzen, H.B.; Ölmez, Ü.; Fagerhol, M.K.; Munthe, E. The leukocyte protein L1 in plasma and synovial fluid from patients with rheumatoid arthritis and osteoarthritis. Scand. J. Rheumatol. 1991, 20, 74–82.
  13. Zhu, Q.; Li, F.; Wang, J.; Ma, J.; Sheng, X. Upregulation of calprotectin in mild IgE-mediated ovalbumin hypersensitivity. Oncotarget 2017, 8, 7342–37354.
  14. Henke, M.O.; Renner, A.; Rubin, B.K.; Gyves, J.I.; Lorenz, E.; Koo, J.S. UP-regulation of S100A8 and S100A9 protein in bronchial epithelial cells by lipopolysaccharide. Exp. Lung Res. 2006, 32, 331–347.
  15. Smith, M.E.; Stockfelt, M.; Tengvall, S.; Bergman, P.; Linden, A.; Qvarfordt, I. Endotoxin exposure increases LL-37—But not calprotectin—In healthy human airways. J. Innate Immun. 2017, 9, 475–482.
  16. De Jong, H.K.; Achouiti, A.; Koh, G.C.; Parry, C.M.; Baker, S.; Faiz, M.A.; van Dissel, J.T.; Vollaard, A.M.; van Leeuwen, E.M.; Roelofs, J.J.; et al. Expression and function of S100A8/A9 (calprotectin) in human typhoid fever and the murine Salmonella model. PLoS Negl Trop Dis. 2015, 9, e0003663.
  17. Gutjahr, E.; Madea, B. Inflammatory reaction patterns of the lung as a response to alveolar hypoxia and their significance for the diagnosis of asphyxiation. Forensic Sci. Int. 2019, 297, 315–325.
  18. Van Zoelen, M.A.D.; Vogl, T.; Foell, D.; Van Veen, S.Q.; Van Till, J.W.O.; Florquin, S.; Tanck, M.W.; Wittebole, X.; Laterre, P.-F.; Boermeester, M.A.; et al. Expression and role of myeloid-related protein-14 in clinical and experimental sepsis. Am. J. Respir. Crit. Care Med. 2009, 180, 1098–1106.
  19. Lipcsey, M.; Hanslin, K.; Stålberg, J.; Smekal, D.; Larsson, A. The time course of calprotectin liberation from human neutrophil granulocytes after Escherichia coli and endotoxin challenge. Innate Immun. 2019, 25, 369–373.
  20. Zwadlo, G.; Brüggen, J.; Gerhards, G.; Schlegel, R.; Sorg, C. Two calcium-binding proteins associated with specific stages of myeloid cell differentiation are expressed by subsets of macrophages in inflammatory tissues. Clin. Exp. Immunol. 1988, 72, 510–515.
  21. Hirvonen, J.; Kortelainen, M.L.; Huttunen, P. Pulmonary and serum surfactant phospholipids and serum catecholamines in strangulation. An experimental study on rats. Forensic Sci. Int. 1997, 90, 17–24.
  22. Ikeno, K.; Koike, K.; Fukuromoto, T.; Shimizu, T.; Nagatomo, M.; Korniyama, A. Increased macrophage-colony stimulating factor levels in neonates with perinatal complications. Early Hum. Dev. 1996, 46, 229–237.
  23. Croce, K.; Gao, H.; Wang, Y.; Mooroka, T.; Sakuma, M.; Shi, C.; Sukhova, G.K.; Packard, R.R.; Hogg, N.; Libby, P.; et al. Myeloid-related protein-8/14 is critical for the biological response to vascular injury. Circulation 2009, 120, 427–436.
  24. Niemelä, M.; Niemelä, O.; Bloigu, R.; Bloigu, A.; Kangastupa, P.; Juvonen, T. Serum calprotectin, a marker of neutrophil activation, and other mediators of inflammation in response to various types of extreme physical exertion in healthy volunteers. J. Inflamm. Res. 2020, 13, 223–231.
  25. Voganatsi, A.; Panyutich, A.; Miyasaki, K.T.; Murthy, R.K. Mechanism of extracellular release of human neutrophil calprotectin complex. J. Leukoc. Biol. 2001, 70, 130–134.
  26. Tardif, M.R.; Chapeton-Montes, J.A.; Posvandzic, A.; Pagé, N.; Gilbert, C.; Tessier, P.A. Secretion of S100A8, S100A9, and S100A12 by neutrophils involves reactive oxygen species and potassium efflux. J. Immunol. Res. 2015, 2015, 1–16.
  27. Stroncek, D.F.; Shankar, R.A.; Skubitz, K.M. The subcellular distribution of myeloid-related protein 8 (MRP8) and MRP14 in human neutrophils. J. Transl. Med. 2005, 3, 36.
  28. Hetland, G.; Talgo, G.J.; Fagerhol, M.K. Chemotaxins C5a and fMLP induce release of calprotectin (leucocyte L1 protein) from polymorphonuclear cells in vitro. Mol. Pathol. 1998, 51, 143–148.
  29. Lominadze, G.; Rane, M.J.; Merchant, M.; Cai, J.; Ward, R.A.; McLeish, K.R. Myeloid-related protein-14 is a p38 MAPK sub-strate in human neutrophils. J. Immunol. 2005, 17, 7257–7267.
  30. Guignard, F.; Mauel, J.; Markert, M. Phosphorylation of myeloid-related proteins MRP-14 and MRP-8 during human neutrophil activation. Eur. J. Biochem. 1996, 241, 265–271.
  31. Seelenmeyer, C.; Stegmayer, C.; Nickel, W. Unconventional secretion of fibroblast growth factor 2 and galectin-1 does not require shedding of plasma membrane-derived vesicles. FEBS Lett. 2008, 58, 1362–1368.
  32. Urban, C.F.; Ermert, D.; Schmid, M.; Abu-Abed, U.; Goosmann, C.; Nacken, W.; Brinkmann, V.; Jungblut, P.R.; Zychlinsky, A. Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida al-bicans. PLoS Pathog. 2009, 5, e1000639.
  33. Lügering, N.; Kucharzik, T.; Lügering, A.; Winde, G.; Sorg, C.; Domschke, W.; Stoll, R. Importance of combined treatment with IL-10 and IL-4, but not IL-13, for inhibition of monocyte release of the Ca(2+)-binding protein MRP8/14. Immunology 1997, 91, 30–34.
  34. Suryono Kido, J.-I.; Hayashi, N.; Kataoka, M.; Shinohara, Y.; Nagata, T. Norepinephrine stimulates calprotectin expression in human monocytic cells. J. Periodontal Res. 2006, 41, 159–164.
  35. Rammes, A.; Roth, J.; Goebeler, M.; Klempt, M.; Hartmann, M.; Sorg, C. Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway. J. Biol. Chem. 1997, 272, 9496–9502.
  36. Wang, S.; Song, R.; Wang, Z.; Jing, Z.; Wang, S.; Ma, J. S100A8/A9 in inflammation. Front. Immunol. 2018, 9, 1298.
  37. Tsai, S.-Y.; Segovia, J.A.; Chang, T.-H.; Morris, I.R.; Berton, M.T.; Tessier, P.A.; Tardif, M.R.; Cesaro, A.; Bose, S. DAMP molecule S100A9 acts as a molecular pattern to enhance inflammation during Influenza A virus infection: Role of DDX21-TRIF-TLR4-MyD88 pathway. PLOS Pathog. 2014, 10, e1003848.
  38. Frosch, M.; Strey, A.; Vogl, T.; Wulffraat, N.M.; Kuis, W.; Sunderkötter, C.; Harms, E.; Sorg, C.; Roth, J. Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum. 2000, 43, 628–637.
  39. Mahnke, K.; Bhardwaj, R.; Sorg, C. Heterodimers of the calcium-binding proteins MRP8 and MRP14 are expressed on the surface of human monocytes upon adherence to fibronectin and collagen. Relation to TNF-α, IL-6, and superoxide production. J. Leukoc. Biol. 1995, 53, 63–71.
  40. Nakashige, T.G.; Zygiel, E.M.; Drennan, C.L.; Nolan, E.M. Nickel sequestration by the host-defense protein human calprotectin. J. Am. Chem. Soc. 2017, 139, 8828–8836.
  41. Achouiti, A.; Vogl, T.; Endeman, H.; Mortensen, B.L.; Laterre, P.F.; Wittebole, X.; van Zoelen, M.A.; Zhang, Y.; Hoogerwerf, J.J.; Florquin, S.; et al. My-eloid-related protein-8/14 facilitates bacterial growth during pneumococcal pneumonia. Thorax 2014, 69, 1034–1042.
  42. Longbottom, D.; Sallenave, J.-M.; Van Heyningen, V. Subunit structure of calgranulins A and B obtained from sputum, plasma, granulocytes and cultured epithelial cells. Biochim. Biophys. Acta 1992, 1120, 215–222.
  43. Huang, S.; Feng, C.; Chen, L.; Huang, Z.; Zhou, X.; Li, B.; Wang, L.-L.; Chen, W.; Lv, F.-Q.; Li, T.-S. Molecular mechanisms of mild and severe pneumonia: Insights from RNA sequencing. Med. Sci. Monit. 2017, 23, 1662–1673.
  44. Raquil, M.-A.; Anceriz, N.; Rouleau, P.; Tessier, P.A. Blockade of antimicrobial proteins S100A8 and S100A9 inhibits phagocyte migration to the alveoli in streptococcal pneumonia. J. Immunol. 2008, 180, 3366–3374.
  45. Corbin, B.D.; Seeley, E.H.; Raab, A.; Feldmann, J.; Miller, M.R.; Torres, V.J.; Anderson, K.L.; Dattilo, B.M.; Dunman, P.M.; Gerads, R.; et al. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science 2008, 319, 962–965.
  46. Diaz-Ochoa, V.E.; Lam, D.; Lee, C.S.; Klaus, S.; Behnsen, J.; Liu, J.Z.; Chim, N.; Nuccio, S.P.; Rathi, S.G.; Mastroianni, J.R.; et al. Salmonella mitigates oxidative stress and thrives in the inflamed gut by evading calprotectin-mediated manganese sequestration. Cell Host Microbe 2016, 19, 814–825.
  47. Hadley, R.C.; Gagnon, D.M.; Brophy, M.B.; Gu, Y.; Nakashige, T.G.; Britt, R.D.; Nolan, E.M. Biochemical and spectroscopic observation of Mn(II) sequestration from bacterial Mn(II) transport machinery by calprotectin. J. Am. Chem. Soc. 2017, 140, 110–113.
  48. Hood, M.I.; Mortensen, B.L.; Moore, J.L.; Zhang, Y.; Kehl-Fie, T.E.; Sugitani, N.; Chazin, W.J.; Caprioli, R.M.; Skaar, E.P. Identification of an Acinetobacter baumannii zinc acquisition system that facilitates resistance to calprotectin-mediated zinc sequestration. PLoS Pathog. 2012, 8, e1003068.
  49. De Filippo, K.; Neill, D.R.; Mathies, M.; Bangert, M.; McNeill, E.; Kadioglu, A.; Hogg, N. A new protective role for S100A9 in regulation of neutrophil recruitment during invasive pneumococcal pneumonia. FASEB J. 2014, 28, 3600–3608.
  50. Bühling, F.; Ittenson, A.; Kaiser, D.; Thölert, G.; Hoffmann, B.; Reinhold, D.; Ansorge, S.; Welte, T. MRP8/MRP14, CD11b and HLA-DR expression of alveolar macrophages in pneumonia. Immunol. Lett. 2000, 71, 185–190.
  51. Moore, J.L.; Becker, K.W.; Nicklay, J.J.; Boyd, K.L.; Skaar, E.P.; Caprioli, R.M. Imaging mass spectrometry for assessing temporal proteomics: Analysis of calprotectin in Acinetobacter baumannii pulmonary infection. Proteomics 2014, 14, 820–828.
  52. Glaros, T.G.; Blancett, C.D.; Bell, T.M.; Natesan, M.; Ulrich, R.G. Serum biomarkers of Burkholderia mallei infection elucidated by proteomic imaging of skin and lung abscesses. Clin. Proteom. 2015, 12, 7.
  53. Mikacenic, C.; Moore, R.; Dmyterko, V.; West, T.E.; Altemeier, W.A.; Liles, W.C.; Lood, C. Neutrophil extracellular traps (NETs) are increased in the alveolar spaces of patients with ventilator-associated pneumonia. Crit. Care 2018, 22, 35.
  54. Kuipers, M.T.; Vogl, T.; Aslami, H.; Jongsma, G.; van den Berg, E.; Vlaar, A.P.J.; Roelofs, J.J.T.H.; Juffermans, N.P.; Schultz, M.J.; van der Poll, T.; et al. High levels of S100A8/A9 proteins aggravate ventilator-induced lung injury via TLR4 signaling. PLoS ONE 2013, 8, e68694.
  55. Hiroshima, Y.; Hsu, K.; Tedla, N.; Chung, Y.M.; Chow, S.; Herbert, C.; Geczy, C.L. S100A8 Induces IL-10 and protects against acute lung injury. J. Immunol. 2014, 192, 2800–2811.
  56. Jerkic, S.P.; Michel, F.; Donath, H.; Herrmann, E.; Schubert, R.; Rosewich, M.; Zielen, S. Calprotectin as a new sensitive marker of neutrophilic inflammation in patients with bronchiolitis obliterans. Mediat. Inflamm. 2020, 2020, 1–7.
  57. Karadjian, G.; Fercoq, F.; Pionnier, N.; Vallarino-Lhermitte, N.; Lefoulon, E.; Nieguitsila, A.; Specht, S.; Carlin, L.M.; Martin, C. Migratory phase of Litomosoides sigmodontis filarial infective larvae is associated with pathology and transient increase of S100A9 expressing neutrophils in the lung. PLoS Negl. Trop. Dis. 2017, 11, e0005596.
  58. Contreras, I.; Shio, M.T.; Cesaro, A.; Tessier, P.A.; Olivier, M. Impact of neutrophil-secreted myeloid related proteins 8 and 14 (MRP 8/14) on leishmaniasis progression. PLoS Negl. Trop. Dis. 2013, 7, e2461.
  59. Pechkovsky, D.V.; Zalutskaya, O.M.; Ivanov, G.I.; Misuno, N.I. Calprotectin (MRP8/14 protein complex) release during my-cobacterial infection in vitro and in vivo. FEMS Immunol. Med. Microbiol. 2000, 29, 27–33.
  60. Zhou, J. Early diagnosis of pulmonary tuberculosis using serum biomarkers. Proteomics 2015, 15, 6–7.
  61. Xu, D.; Li, Y.; Li, X.; Wei, L.L.; Pan, Z.; Jiang, T.T.; Chen, Z.L.; Wang, C.; Cao, W.M.; Zhang, X.; et al. Serum protein S100A9, SOD3, and MMP9 as new diagnostic biomarkers for pulmonary tuberculosis by iTRAQ-coupled two-dimensional LC-MS/MS. Proteomics 2015, 15, 58–67.
  62. Gopal, R.; Monin, L.; Torres, D.; Slight, S.; Mehra, S.; McKenna, K.C.; Fallert Junecko, B.A.; Reinhart, T.A.; Kolls, J.; Báez-Saldaña, R.; et al. S100A8/A9 Proteins mediate neutrophilic inflammation and lung pathology during tuberculosis. Am. J. Respir. Crit. Care Med. 2013, 188, 1137–1146.
  63. Liu, Q.; Pan, L.; Han, F.; Luo, B.; Jia, H.; Xing, A.; Li, Q.; Zhang, Z. Proteomic profiling for plasma biomarkers of tuberculosis progression. Mol. Med. Rep. 2018, 18, 1551–1559.
  64. Delabie, J.; de Wolf-Peeters, C.; van den Oord, J.J.; Desmet, V.J. Differential expression of the calcium-binding proteins MRP8 and MRP14 in granulomatous conditions: An immunohistochemical study. Clin. Exp. Immunol. 1990, 81, 123–126.
  65. Wang, J.; Huang, C.; Wu, M.; Zhong, Q.; Yang, K.; Li, M.; Zhan, X.; Wen, J.; Zhou, L.; Huang, X. MRP8/14 induces autophagy to eliminate intracellular Mycobacterium bovis BCG. J. Infect. 2015, 70, 415–426.
  66. Larsson, G.; Shenoy, K.T.; Ramasubramanian, R.; Thayumanavan, L.; Balakumaran, L.K.; Bjune, G.A.; Moum, B.A. High faecal calprotectin levels in intestinal tuberculosis are associated with granulomas in intestinal biopsies. Infect. Dis. 2015, 47, 137–143.
  67. Larsson, G.; Shenoy, K.T.; Ramasubramanian, R.; Thayumanavan, L.; Balakumaran, L.K.; Bjune, G.A.; Moum, B.A. Faecal calprotectin levels differentiate intestinal from pulmonary tuberculosis: An observational study from Southern India. United Eur. Gastroenterol. J. 2014, 2, 397–405.
  68. Ma, J.; Zhao, F.; Su, W.; Li, Q.; Li, J.; Ji, J.; Deng, Y.; Zhou, Y.; Wang, X.; Yang, H.-M.; et al. Zinc finger and interferon-stimulated genes play a vital role in TB-IRIS following HAART in AIDS. Pers. Med. 2018, 15, 251–269.
  69. García de Guadiana, R.L.; Mulero, M.D.R.; Olivo, M.H.; Rojas, C.R.; Arenas, V.R.; Morales, M.G.; Abellán, A.B.; Conesa-Zamora, P.; García-García, J.; Hernández, A.C.; et al. Circulating levels of GDF-15 and calprotectin for prediction of in-hospital mortality in COVID-19 patients: A case series. J. Infect. 2020, S0163–4453(20)30543-0.
  70. Silvin, A.; Chapuis, N.; Dunsmore, G.; Goubet, A.-G.; Dubuisson, A.; DeRosa, L.; Almire, C.; Hénon, C.; Kosmider, O.; Droin, N.; et al. Elevated calprotectin and abnormal myeloid cell subsets discriminate severe from mild COVID-19. Cell 2020, 182, 1401–1418.
  71. Shi, H.; Zuo, Y.; Yalavarthi, S.; Gockman, K.; Zuo, M.; Madison, J.A.; Blair, C.; Woodward, W.; Lezak, S.P.; Lugogo, N.L.; et al. Neutrophil calprotectin identifies severe pulmonary disease in COVID-19. J. Leukoc. Biol. 2020, 109, 67–72.
  72. Petito, E.; Falcinelli, E.; Paliani, U.; Cesari, E.; Vaudo, G.; Sebastiano, M.; Cerotto, V.; Guglielmini, G.; Gori, F.; Malvestiti, M.; et al. COVIR study investigators. Neutrophil more than platelet activation associates with thrombotic complications in COVID-19 patients. J. Infect. Dis 2020, jiaa756.
  73. Effenberger, M.; Grabherr, F.; Mayr, L.; Schwaerzler, J.; Nairz, M.; Seifert, M.; Hilbe, R.; Seiwald, S.; Scholl-Buergi, S.; Fritsche, G.; et al. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut 2020, 69, 1543–1544.
  74. Ojetti, V.; Saviano, A.; Covino, M.; Acampora, N.; Troiani, E.; Franceschi, F.; GEMELLI AGAINST COVID-19 Group. COVID-19 and intestinal inflammation: Role of fecal calprotectin. Dig. Liver Dis. 2020, 52, 1231–1233.
  75. Mago, S.; Vaziri, H.; Tadros, M. The utility of fecal calprotectin in the era of COVID-19 pandemic. Gastroenterology 2020, S0016–5085(20)30678-8.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Others
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Ourania S. Kotsiou
View Times: 471
Revisions: 3 times (View History)
Update Date: 26 Feb 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback