Phospholipase C and perfringolysin O from Clostridium perfringens upregulate 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 (PFO) differentially induced human umbilical vein endothelial cell expression and synthesis of endothelial cell-leukocyte adherence molecule-1 (ELAM-1), intracellular leukocyte adherence molecule-1 (ICAM-1), and interleukin-8 (IL-8). PLC strongly induced expression of ELAM-1, ICAM-1, and IL-8, while PFO stimulated early ICAM-1 expression but did not promote 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 activational proteins and direct cytopathic effects may contribute to the leukostasis, vascular compromise, and capillary leak characteristics of C. perfringens gas gangrene.
Bryant
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Infectious Diseases Section, VA Medical Center, Boise, Idaho 83702, USA.
Stevens
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D001427:Bacterial Toxins / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D003016:Clostridium perfringens / Q000201:enzymology / Q000472:pathogenicity*; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005098:Exotoxins / Q000494:pharmacology*; D006460:Hemolysin Proteins; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis*; D010738:Type C Phospholipases / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation
D001427:Bacterial Toxins; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D005098:Exotoxins; D006460:Hemolysin Proteins; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; C020452:Clostridium perfringens theta-toxin; D010738:Type C Phospholipases