ADHERENCE OF NEUTROPHILS TO HUMAN PERITONEAL MESOTHELIAL CELLS - ROLEOF INTERCELLULAR-ADHESION MOLECULE-1

Peritonitis is accompanied by a massive influx of polymorphonuclear le ukocytes (PMN) into the peritoneal cavity, little is known, however, a bout the process of neutrophil transmigration across the peritoneal me mbrane, The study presented here, therefore, investigates the adherenc e of human PMN to human peritoneal mesothelial cell monolayers and exa mines the importance of intercellular adhesion molecule-1 (ICAM-1) in the process. Human peritoneal mesothelial cells (HPMC) constitutively expressed ICAM-1 protein and mRNA. Stimulation with IL-1 beta or TNF a lpha resulted in time- and dose-dependent upregulation of ICAM-1 mRNA transcript and increased cell-surface immunoreactive protein expressio n, Peak surface expression of ICAM-1 occurred between 12 and 24 h afte r cytokine stimulation when the level of expression was increased by o n average threefold above control. The adherence of PMN to HPMC after stimulation with either IL-1 beta or TNF alpha was both dose- and time -dependent. Peaks of PMN binding to HPMC occurred at 2 and 12 h after stimulation. After 12 h, the number of PMN binding to HPMC increased f rom 71.3 +/- 12.5 in control cells to 180 +/- 36.5 and 125 +/- 23.6 (x 10(3) PMN), after IL-1 beta (100 pg/mL) and TNF alpha (1000 pg/mL), r espectively (z = 2.52 and 2.38, N = 6, P < 0.02 versus control for bot h). The roles of HPMC ICAM-1 and the PMN counter receptor LFA-1 (CD11a /CD18) in the adherence of PMN to HPMC were confirmed by using anti-CA M Fab'(2) fragments, and anti-integrin antibodies, all of which signif icantly reduced the adherence of PMN to both control and cytokine-trea ted HPMC, These data suggest that ICAM-1 expression by HPMC may be one mechanism by which neutrophils adhere to the mesothelium during their transmigration into the inflamed peritoneal cavity.