title: Clostridial gas gangrene. I. Cellular and molecular mechanisms of microvascular dysfunction induced by exotoxins of Clostridium perfringens.
abstract: Mechanisms responsible for the rapid tissue destruction in gas gangrene are not well understood. To examine the early effects of Clostridium perfringens exotoxins on tissue perfusion, a rat model of muscle blood flow was developed. Intramuscular injection of a clostridial toxin preparation containing both phospholipase C (PLC) and theta-toxin caused a rapid (1-2 min) and irreversible decrease in blood flow that paralleled formation of activated platelet aggregates in venules and arterioles. Later (20-40 min), aggregates contained fibrin and leukocytes, and neutrophils accumulated along vascular walls. Flow cytometry confirmed that these clostridial toxins or recombinant PLC induced formation of P-selectin-positive platelet aggregates. Neutralization of PLC activity in the clostridial toxin preparation completely abrogated human platelet responses and reduced perfusion deficits. It is concluded that tissue destruction in gas gangrene is related to profound attenuation of blood flow initiated by activation of platelet responses by PLC.
authors.affiliation: VA Medical Center, Infectious Diseases Section, Boise, ID 83702, USA. abryant@micron.net
authors.forename: A E
authors.initials: AE
authors.lastname: Bryant
authors.forename: R Y
authors.initials: RY
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Nagata
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: C H
authors.initials: CH
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Finegold
authors.forename: P H
authors.initials: PH
authors.lastname: Guth
authors.forename: D L
authors.initials: DL
authors.lastname: Stevens
mesh_terms: D000818:Animals; D003016:Clostridium perfringens; D005098:Exotoxins / Q000378:metabolism*; D005434:Flow Cytometry; D005738:Gas Gangrene / Q000503:physiopathology*; D006801:Humans; D008833:Microcirculation; D009132:Muscles / Q000098:blood supply*; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation; D051381:Rats; D012039:Regional Blood Flow; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D005098:Exotoxins; D019007:P-Selectin; D010738:Type C Phospholipases