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.