LIPOPOLYSACCHARIDE INDUCES HYPERADHESION OF ENDOTHELIAL-CELLS FOR NEUTROPHILS LEADING TO DAMAGE

Adhesion of polymorphonuclear leukocytes (PMN) to endothelial cells is an early key event in the inflammatory response and plays an importan t part in the pathogenesis of septic shock, contributing to vascular a nd tissue injury. Lipopolysaccharides (LPS) activate endothelial cells to enhanced expression of adhesion molecules. We investigated the int eraction of human PMN with resting and LPS-activated human umbilical v ein endothelial cells. The activation of endothelial cells by LPS alon e did not lead to direct functional or morphological changes as measur ed by detachment of the endothelial cells from a monolayer and transen dothelial albumin flux. LPS induced an increased adhesion of unstimula ted PMN to endothelial cells. This was accompanied by endothelial deta chment and increased permeability across a monolayer. Endothelial cell lysis as measured by Cr-51 release was unaffected. Stimulation of PMN with phorbol ester did not further increase adherence, detachment, or permeability. We conclude that LPS activates endothelial cells and re nders cultured monolayers more susceptible to PMN-induced damage. This may provide further insight into the relationship between PMN activat ion and endothelial damage in Gram-negative sepsis.