COMBINATORIAL REQUIREMENTS FOR ADHESION MOLECULES IN MEDIATING NEUTROPHIL EMIGRATION DURING BACTERIAL PERITONITIS IN MICE

To investigate the requirements for adhesion molecules in neutrophil e migration 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 antibo dies against ICAM-1 or genetic deficiency of ICAM-1, Anti-CD11a/CD18 a ntibodies decreased emigration in ICAM-1 mutant mice, suggesting that ICAM-1 independent emigration requires CD11/CD18 complexes, In contras t, mice mutant in ICAM-1 plus E-selectin showed no defect in emigratio n, suggesting that E-selectin commits neutrophils to an ICAM-1-depende nt pathway during streptococcal peritonitis, However, in mutant mice l acking 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 p eritoneal inflammation. After 24 h of peritonitis, there were no diffe rences between WT and E-selectin/P-selectin/ICAM-1 mutant mice, demons trating that these endothelial adhesion molecules are not essential to neutrophil emigration during later stages of peritonitis.