Damage-Associated Molecular Pattern S100A9 Increases Bactericidal Activity of Human Neutrophils by Enhancing Phagocytosis

Simard, Jean-Christophe; Simon, Marie-Michelle; Tessier, Philippe A.; Girard, Denis

doi:10.4049/jimmunol.1002956

Cited by 97 publications

(93 citation statements)

References 70 publications

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“…17,22,24,57,58 CLP also causes the degranulation of PMNs and the release of MMPs and collagenases, thus contributing to cartilage degradation. 59 Osteoclast differentiation is also affected by CLP primarily through a TLR4-mediated signal and S100A8-induced osteoclastic bone resorption in a murine model. 60 CLP levels are higher in the serum of RA patients compared with healthy subjects or patients with osteoarthritis (OA), spondyloarthritis (SpA), systemic lupus erythematosus (SLE), and pseudogout.…”

Section: Clp In Rheumatic Diseasesmentioning

confidence: 98%

Calprotectin in rheumatic diseases

Ometto

Friso

Astorri

et al. 2016

Exp Biol Med (Maywood)

139

105

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Calprotectin is an acute-phase protein produced by monocytes and neutrophils in the circulation and inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to detect minimal residual inflammation and is a candidate biomarker in inflammatory diseases. High serum levels are associated with some severe manifestations of rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin levels in other fluids, such as saliva and synovial fluid, might be helpful in the diagnosis of rheumatic diseases. Of interest is also the potential role of calprotectin as a target of treatment. AbstractCalprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-a inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker.

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Section: Clp In Rheumatic Diseasesmentioning

confidence: 98%

Calprotectin in rheumatic diseases

Ometto

Friso

Astorri

et al. 2016

Exp Biol Med (Maywood)

139

105

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“…SRBCs were washed three time in ice-cold PBS, resuspended at 50 3 10 6 cells/ml, and then opsonized with anti-SRBC Ab (1:200) at 37˚C for 45 min, as documented previously (21). THP-1 cells (10 3 10 6 /ml) or monocytes (5 3 10 6 cells/ml) were treated with the agonists indicated in the corresponding figure legends in RPMI 1640 medium for 30 min.…”

Section: Phagocytosis Assaymentioning

confidence: 99%

IL-21 Enhances Phagocytosis in Mononuclear Phagocyte Cells: Identification of Spleen Tyrosine Kinase as a Novel Molecular Target of IL-21

Vallières

Girard

2013

The Journal of Immunology

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The biological significance of the IL-21/IL-21R system in human monocytes/macrophages is not well documented, and the expression of IL-21R is unclear and has been disputed. In this study, we showed for the first time, to our knowledge, that human monocyte–like THP-1 cells expressed the two IL-21R components, CD132 (γc) and IL-21Rα, on their cell surface, as assessed by flow cytometry. Moreover, IL-21 was found to enhance FcR-mediated phagocytosis, but not endocytosis. The ability of IL-21 to enhance phagocytosis was not associated with an increased expression of both IL-21R components at the cell surface, and IL-21 did not act in synergy with IL-15. IL-21 activated spleen tyrosine kinase (Syk), as evidenced by its ability to increase Syk phosphorylation. Using a pharmacological approach to inhibit Syk activity, and an antisense technique to downregulate Syk protein expression, we demonstrated the importance of Syk in IL-21–induced phagocytosis. In addition, both CD132 and IL-21Rα were expressed on the cell surface of naive monocytes, as well as in GM-CSF–monocyte-derived macrophages. Moreover, IL-21 also induced phagocytosis in these cells. We conclude that IL-21 possesses important biological effects in mononuclear phagocyte cells and that Syk is a novel molecular target of IL-21 that was previously unknown. Therefore, future development of therapeutic strategies targeting the IL-21/IL-21R system should consider that monocyte and macrophage cell physiology may be affected by this system.

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“…An antimicrobial activity for MRP-14, in association with MRP-8 (calprotectin; L1 myelomonocytic antigen), has been described many years ago [3,4]. Furthermore, other biologic activities have been attributed to MRP-14, alone or in association with MRP-8, for example, effects on neutrophils, including induction of chemotaxis, adhesion to extracellular matrix proteins, degranulation, and enhancement of phagocytosis [8,33]. Moreover, MRP-14 has been implied as an antiapoptotic molecule, fine-tuning the neutrophil turnover [34].…”

Section: Mrp-14 In the Peripheral Blood Of Patients With Infection Anmentioning

confidence: 99%

“…Antimicrobial activities have been attributed to the complex of MRP-14/MRP-8 [3,4], and a variety of biologic activities affecting the innate host response has been described. These include chemotaxis for neutrophils, increased cellular adherence through activation of the adhesion molecule CD11b [5,6], growth factor functions [7], or enhanced phagocytosis [8]. MRP-14 is found in the peripheral blood of patients with inflammatory diseases, such as rheumatoid arthritis or inflammatory bowel disease (reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil-derived MRP-14 is up-regulated in infectious osteomyelitis and stimulates osteoclast generation

Dapunt

Giese

Maurer

et al. 2015

Journal of Leukocyte Biology

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Bone infections of patients with joint replacement by endoprosthesis (so called “periprosthetic joint infection”) pose a severe problem in the field of orthopedic surgery. The diagnosis is often difficult, and treatment is, in most cases, complicated and prolonged. Patients often require an implant exchange surgery, as the persistent infection and the accompanying inflammation lead to tissue damage with bone degradation and consequently, to a loosening of the implant. To gain insight into the local inflammatory process, expression of the proinflammatory cytokine MRP-14, a major content of neutrophils, and its link to subsequent bone degradation was evaluated. We found MRP-14 prominently expressed in the affected tissue of patients with implant-associated infection, in close association with the chemokine CXCL8 and a dense infiltrate of neutrophils and macrophages. In addition, the number of MRP-14-positive cells correlated with the presence of bone-resorbing osteoclasts. MRP-14 plasma concentrations were significantly higher in patients with implant-associated infection compared with patients with sterile inflammation or healthy individuals, advocating MRP-14 as a novel diagnostic marker. A further biologic activity of MRP-14 was detected: rMRP-14 directly induced the differentiation of monocytes to osteoclasts, thus linking the inflammatory response in implant infections with osteoclast generation, bone degradation, and implant loosening.

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Damage-Associated Molecular Pattern S100A9 Increases Bactericidal Activity of Human Neutrophils by Enhancing Phagocytosis

Cited by 97 publications

References 70 publications

Calprotectin in rheumatic diseases

Calprotectin in rheumatic diseases

IL-21 Enhances Phagocytosis in Mononuclear Phagocyte Cells: Identification of Spleen Tyrosine Kinase as a Novel Molecular Target of IL-21

Neutrophil-derived MRP-14 is up-regulated in infectious osteomyelitis and stimulates osteoclast generation

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