Mizgerd J P, Quinlan W M, LeBlanc B W, Kutkoski G J, Bullard D C, Beaudet A L, Doerschuk C M
Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
J Leukoc Biol. 1998 Sep;64(3):291-7. doi: 10.1002/jlb.64.3.291.
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.
为了研究腹膜炎期间中性粒细胞渗出过程中黏附分子的需求，给小鼠腹腔注射肺炎链球菌，同时阻断多种黏附分子的功能。4小时后的渗出受到抗ICAM-1抗体或ICAM-1基因缺陷的影响。抗CD11a/CD18抗体减少了ICAM-1突变小鼠的渗出，表明不依赖ICAM-1的渗出需要CD11/CD18复合物。相比之下，ICAM-1和E-选择素双突变的小鼠在渗出方面没有缺陷，这表明在链球菌性腹膜炎期间，E-选择素使中性粒细胞进入依赖ICAM-1的途径。然而，在缺乏三种内皮黏附分子E-选择素、P-选择素和ICAM-1的突变小鼠中，4小时后的渗出明显受损。因此，P-选择素对于不依赖ICAM-1和E-选择素的急性腹膜炎症至关重要。腹膜炎24小时后，野生型小鼠和E-选择素/P-选择素/ICAM-1突变小鼠之间没有差异，这表明这些内皮黏附分子在腹膜炎后期对中性粒细胞渗出不是必需 的。
