Potentiation of Endothelium Directed Immune Complex-Mediated Cytotoxicity of Neutrophils by Cytokine Activation of the Endothelial Monolayers: A New in Vitro Model for Leukoclastic Vasculitis

Abstract

Polymorphonuclear neutrophils (PMN), which display intense spreading and metabolic activation on plastic tissue culture dishes (Dahinden, C. et aL, 1983a; Dahinden, C. et al., 1983b), showed only loose attachment to endothelial cell monolayers (ECML) without any measurable metabolic activation and cytotoxicity (Fehr, J. et al., 1985). In the light that endothelial cells stimulated with IL-1 and TNF actively control adherence and transendothelial migration in the absence of a chemotactic gradient (4), metabolic activation of the interacting PMN was of interest. The endothelial-dependent type of adherence is characterized by intense interaction of the PMN membrane with the activated endothelium (Moser, R. et al., 1989). Such tight cell contact is, in terms of sheer stress resistance, comparable to the cell substrate interaction of PMN spreading on artificial surfaces which results in severe metabolic activation and degranulation (Dahinden, C. et al., 1983a; Dahinden, C. et al., 1983b). However, the endothelial-dependent adherence had no influence on the PMN metabolic activity (Moser, R. et al., 1989).