title: Combinatorial requirements for adhesion molecules in mediating neutrophil emigration during bacterial peritonitis in mice.
abstract: To investigate the requirements for adhesion molecules in neutrophil emigration during peritonitis, mice received intraperitoneal injections of Streptococcus pneumoniae while the functions of multiple adhesion molecules were blocked. Emigration after 4 h was compromised by antibodies against ICAM-1 or genetic deficiency of ICAM-1. Anti-CD11a/CD18 antibodies decreased emigration in ICAM-1 mutant mice, suggesting that ICAM-1 independent emigration requires CD11/CD18 complexes. In contrast, mice mutant in ICAM-1 plus E-selectin showed no defect in emigration, suggesting that E-selectin commits neutrophils to an ICAM-1-dependent pathway during streptococcal peritonitis. However, in mutant mice lacking the three endothelial adhesion molecules E-selectin, P-selectin, and ICAM-1, emigration after 4 h was significantly compromised. Thus, P-selectin is essential to ICAM-1- and E-selectin-independent acute peritoneal inflammation. After 24 h of peritonitis, there were no differences between WT and E-selectin/P-selectin/ICAM-1 mutant mice, demonstrating that these endothelial adhesion molecules are not essential to neutrophil emigration during later stages of peritonitis.
authors.affiliation: Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Mizgerd
authors.forename: W M
authors.initials: WM
authors.lastname: Quinlan
authors.forename: B W
authors.initials: BW
authors.lastname: LeBlanc
authors.forename: G J
authors.initials: GJ
authors.lastname: Kutkoski
authors.forename: D C
authors.initials: DC
authors.lastname: Bullard
authors.forename: A L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: C M
authors.initials: CM
authors.lastname: Doerschuk
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D019040:E-Selectin / Q000235:genetics / Q000276:immunology; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D007958:Leukocyte Count; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D019007:P-Selectin / Q000235:genetics / Q000276:immunology; D010538:Peritonitis / Q000276:immunology* / Q000473:pathology; D011008:Pneumococcal Infections; D013864:Thioglycolates
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D019007:P-Selectin; D013864:Thioglycolates; D018799:Intercellular Adhesion Molecule-1