Blockade of S100A8 and S100A9 Suppresses Neutrophil Migration in Response to Lipopolysaccharide 1

Recently, proinflammatory activities had been described for S100A8 and S100A9, two proteins found at inflammatory sites and within the neutrophil cytoplasm. In this study, we investigated the role of these proteins in neutrophil migration in vivo in response to LPS. LPS was injected into the murine air pouch, which led to the release of S100A8, S100A9, and S100A8/A9 in the pouch exudates that preceded accumulation of neutrophils. Passive immunization against S100A8 and S100A9 led to a 52% inhibition of neutrophil migration in response to LPS at 3 h postinjection. Injection of LPS was also associated with an increase in peripheral blood neutrophils and the presence in serum of S100A9 and S100A8/A9. Intravenous injection of S100A8, S100A9, or S100A8/A9 augmented the number of circulating neutrophils and diminished the number of neutrophils in the bone marrow, demonstrating that S100A8 and S100A9 induced the mobilization of neutrophils from the bone marrow to the blood. Finally, passive immunization with anti-S100A9 inhibited the neutrophilia associated with LPS injection in the air pouch. These results suggest that S100A8 and S100A9 play a role in the inflammatory response to LPS by inducing the release of neutrophils from the bone marrow and directing their migration to the inflammatory site.

[1]  P. Rouleau,et al.  Proinflammatory Activities of S100: Proteins S100A8, S100A9, and S100A8/A9 Induce Neutrophil Chemotaxis and Adhesion 1 , 2003, The Journal of Immunology.

[2]  M. Tremblay,et al.  HIV-1 Transcription and Virus Production Are Both Accentuated by the Proinflammatory Myeloid-Related Proteins in Human CD4+ T Lymphocytes1 , 2002, The Journal of Immunology.

[3]  N. Hogg,et al.  The S100 Family Heterodimer, MRP-8/14, Binds with High Affinity to Heparin and Heparan Sulfate Glycosaminoglycans on Endothelial Cells* , 2002, The Journal of Biological Chemistry.

[4]  N. Hogg,et al.  The Use of Lymphocyte Function–Associated Antigen (Lfa)-1–Deficient Mice to Determine the Role of Lfa-1, Mac-1, and α4 Integrin in the Inflammatory Response of Neutrophils , 2001, The Journal of experimental medicine.

[5]  M. Herzberg,et al.  Calprotectin Expression In Vitro by Oral Epithelial Cells Confers Resistance to Infection by Porphyromonas gingivalis , 2001, Infection and Immunity.

[6]  M. Herzberg,et al.  Calprotectin Expression Inhibits Bacterial Binding to Mucosal Epithelial Cells , 2001, Infection and Immunity.

[7]  Tony S. Tao,et al.  Proinflammatory properties of the human S100 protein S100A12 , 2001, Journal of leukocyte biology.

[8]  C. Geczy,et al.  IL-10 Up-Regulates Macrophage Expression of the S100 Protein S100A81 , 2001, The Journal of Immunology.

[9]  M. Selsted,et al.  Human Neutrophil-Mediated Nonoxidative Antifungal Activity against Cryptococcus neoformans , 2000, Infection and Immunity.

[10]  C. Sorg,et al.  Transendothelial migration of 27E10+ human monocytes. , 2000, International immunology.

[11]  W. Chazin,et al.  Zinc-reversible antimicrobial activity of recombinant calprotectin (migration inhibitory factor-related proteins 8 and 14). , 2000, The Journal of infectious diseases.

[12]  D. Pechkovsky,et al.  Calprotectin (MRP8/14 protein complex) release during mycobacterial infection in vitro and in vivo. , 2000, FEMS immunology and medical microbiology.

[13]  Carolyn L. Geczy,et al.  IFN-γ and TNF Regulate Macrophage Expression of the Chemotactic S100 Protein S100A81 , 2000, The Journal of Immunology.

[14]  N. Wulffraat,et al.  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. , 2000, Arthritis and rheumatism.

[15]  M. Wilkins,et al.  Human Gingival Crevicular Fluid Contains MRP8 (S100A8) and MRP14 (S100A9), Two Calcium-binding Proteins of the S100 Family , 2000, Journal of dental research.

[16]  H. Kolb,et al.  Cutting Edge: Heat Shock Protein 60 Is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex1 , 2000, The Journal of Immunology.

[17]  M. Neurath,et al.  RAGE Mediates a Novel Proinflammatory Axis A Central Cell Surface Receptor for S100/Calgranulin Polypeptides , 1999, Cell.

[18]  P. Ghezzi,et al.  Thioredoxin, a Redox Enzyme Released in Infection and Inflammation, Is a Unique Chemoattractant for Neutrophils, Monocytes, and T Cells , 1999, The Journal of experimental medicine.

[19]  H. Kolb,et al.  Human 60-kDa heat-shock protein: a danger signal to the innate immune system. , 1999, Journal of immunology.

[20]  H. Schluesener,et al.  CP-10, a chemotactic peptide, is expressed in lesions of experimental autoimmune encephalomyelitis, neuritis, uveitis and in C6 gliomas , 1999, Journal of Neuroimmunology.

[21]  P. Sohnle,et al.  Histidine-based zinc-binding sequences and the antimicrobial activity of calprotectin. , 1998, The Journal of infectious diseases.

[22]  N. Hogg,et al.  The human S100 protein MRP-14 is a novel activator of the beta 2 integrin Mac-1 on neutrophils. , 1998, Journal of immunology.

[23]  C. Geczy,et al.  Induction of the S100 chemotactic protein, CP-10, in murine microvascular endothelial cells by proinflammatory stimuli. , 1997, Blood.

[24]  S. McColl,et al.  Chemokine networks in vivo: involvement of C-X-C and C-C chemokines in neutrophil extravasation in vivo in response to TNF-alpha. , 1997, Journal of immunology.

[25]  P. Sohnle,et al.  Inhibition of Candida albicans growth by calprotectin in the absence of direct contact with the organisms. , 1996, The Journal of infectious diseases.

[26]  C. Heizmann,et al.  Amino acid sequence determination of human S100A12 (P6, calgranulin C, CGRP, CAAF1) by tandem mass spectrometry. , 1996, Biochemical and biophysical research communications.

[27]  T. Springer,et al.  Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18. , 1996, Blood.

[28]  R. van Furth,et al.  Heat shock protein 65 induces CD62e, CD106, and CD54 on cultured human endothelial cells and increases their adhesiveness for monocytes and granulocytes. , 1996, Journal of immunology.

[29]  J. M. Graf,et al.  Contribution of LFA-1 and Mac-1 to CD18-dependent neutrophil emigration in a neonatal rabbit model. , 1996, Journal of applied physiology.

[30]  P. Kenny,et al.  Functional chemotactic factor CP-10 and MRP-14 are abundant in murine abscesses , 1996, Infection and immunity.

[31]  M. Lackmann,et al.  S100 protein CP‐10 stimulates myeloid cell chemotaxis without activation , 1996, Journal of cellular physiology.

[32]  K. Schmid,et al.  The myeloic related protein MRP8/14 (27E10 antigen)— usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function , 1995, European journal of clinical investigation.

[33]  P. Sohnle,et al.  Resistance of zinc-supplemented Candida albicans cells to the growth inhibitory effect of calprotectin. , 1995, The Journal of infectious diseases.

[34]  G. Evans.  Removal of blood from laboratory mammals and birds , 1994, Laboratory animals.

[35]  C. Geczy,et al.  Acute inflammatory activity of the S100 protein CP-10. Activation of neutrophils in vivo and in vitro. , 1994, Journal of immunology.

[36]  B. Tümmler,et al.  Complex pattern of the myelo-monocytic differentiation antigens MRP8 and MRP14 during chronic airway inflammation. , 1992, Immunobiology.

[37]  J. Brun,et al.  Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity. , 1992, The Journal of rheumatology.

[38]  R. Moritz,et al.  Purification and structural analysis of a murine chemotactic cytokine (CP-10) with sequence homology to S100 proteins. , 1992, The Journal of biological chemistry.

[39]  P. Sohnle,et al.  The zinc-reversible antimicrobial activity of neutrophil lysates and abscess fluid supernatants. , 1991, The Journal of infectious diseases.

[40]  N. Hogg,et al.  Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. , 1991, The Journal of biological chemistry.

[41]  C. Figarella,et al.  Identification of 'cystic fibrosis protein' as a complex of two calcium-binding proteins present in human cells of myeloid origin. , 1991, Biochimica et biophysica acta.

[42]  E. Lingaas,et al.  Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin , 1990, The Lancet.

[43]  C. Smith,et al.  Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. , 1989, The Journal of clinical investigation.

[44]  N. Hogg,et al.  Monoclonal antibody 5.5 reacts with p8,14, a myeloid molecule associated with some vascular endothelium , 1989, European journal of immunology.

[45]  P. Sohnle,et al.  NEUTROPHIL DEATH AS A DEFENCE MECHANISM AGAINST CANDIDA ALBICANS INFECTIONS , 1988, The Lancet.

[46]  R. Maclennan.  ANTI-VIRUS FOR LEUKAEMIA. , 1964, Lancet.

[47]  M. Hirashima,et al.  This information is current as Macrophages Chemoattractant for Monocytes and Human Galectin-3 Is a Novel , 2000 .

[48]  M. Steinbakk,et al.  The leucocyte protein L1 (calprotectin): a putative nonspecific defence factor at epithelial surfaces. , 1995, Advances in experimental medicine and biology.

[49]  P. Sohnle,et al.  Antimicrobial activity of an abundant calcium-binding protein in the cytoplasm of human neutrophils. , 1991, The Journal of infectious diseases.