Protective effect of plasma in polymorphonuclear neutrophil-mediated cytotoxicity of endothelial cells in the systemic inflammatory response syndrome.

Abstract

Polymorphonuclear neutrophil (PMN)-mediated endothelial cell (EC) cytotoxicity is well described in many in vitro systems. These observations have been extended in vivo and suggest that circulating PMNs adherent to endothelial cells can damage these endothelial cells and produce the capillary leak that is central to the evolution of a systemic inflammatory response to multiple organ failure. However, most PMC-EC interactions in the circulation must occur in the presence of plasma, therefore we studied PMN-induced endothelial cell cytotoxicity in the absence and presence of autologous plasma from healthy human volunteers and patients with the systemic inflammatory response syndrome (SIRS) requiring admission to an intensive care unit. PMNs from patients with SIRS had increased endothelial cell adherence compared with controls, but equivalent endothelial cell cytotoxicity. Endothelial cell activation with TNF-alpha and IL-1beta markedly increased PMN adherence to endothelial cells. Plasma had a minimal effect on the adherence of PMNs to endothelial cells at baseline or after endothelial cell activation. In contrast, plasma provided endothelial cells with almost complete protection from PMN-induced cytotoxicity at baseline, as well as after endothelial cell activation in both human volunteers and patients with SIRS. The data suggest that PMNs may cause cytotoxic damage in end organs such as the lung only after they diapedese through the endothelial barrier into the extracellular matrix removed from the protective effect of circulating plasma.