PHOSPHOLIPASE-C AND PERFRINGOLYSIN-O FROM CLOSTRIDIUM-PERFRINGENS UP-REGULATE ENDOTHELIAL CELL-LEUKOCYTE ADHERENCE MOLECULE-1 AND INTERCELLULAR LEUKOCYTE ADHERENCE MOLECULE-1 EXPRESSION AND INDUCE INTERLEUKIN-8 SYNTHESIS IN CULTURED HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

Clostridium perfringens phospholipase C (PLC) and perfringolysin O (PF O) differentially induced human umbilical vein endothelial cell expres sion and synthesis of endothelial cell-leukocyte adherence molecule-1 (ELAM-1), intercellular leukocyte adherence molecule-1 (ICAM-1), and i nterleukin-8 (1L-8). PLC strongly induced expression of ELAM-1, ICAM-1 , and IL-8, while PFO stimulated early ICAM-1 expression but did not p romote ELAM-1 expression or IL-8 synthesis. PLC caused human umbilical vein endothelial cells to assume a fibroblastoid morphology, whereas PFO, in high concentrations or after prolonged low-dose toxin exposure , caused cell death. The toxin-induced expression of proadhesive and a ctivational proteins and direct cytopathic effects may contribute to t he leukostasis, vascular compromise, and capillary leak characteristic s of C. perfringens gas gangrene.