Pathogenesis of Shiga toxin-associated hemolytic uremic syndrome.
The aim of this review is to examine recent advances in experimental and clinical research relevant to the pathogenesis of diarrhea-associated hemolytic uremic syndrome with special reference to histopathologic findings, virulence factors of Shiga toxin-producing Escherichia coli, the host response, and the prothrombotic state. Despite significant advances during the past decade, the exact mechanism by which Shiga toxin-producing E. coli leads to hemolytic uremic syndrome remains unclear. Factors such as Shiga toxin, lipopolysaccharide, the adhesins intimin and E. coli-secreted proteins A, B, and D, the 60-MD plasmid, and enterohemolysin likely contribute to the pathogenesis. Data on the inflammatory response of the host, including leukocytes and inflammatory mediators, are updated. The pathogenesis of the prothrombotic state leading to thrombocytopenia secondary to endothelial cell damage and platelet activation is also discussed. A hypothetical sequence of events from ingestion of the bacteria to the development of full-blown hemolytic uremic syndrome is proposed.
Proulx
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F
Department of Pediatrics, Sainte-Justine Hospital, University of Montreal, 3175 Chemin Côte Sainte-Catherine, Montreal, Canada, H3T-1C5. fproulx_01@yahoo.ca
Seidman
E G
EG
Karpman
D
D
D018829:Adhesins, Bacterial / Q000633:toxicity; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity; D003967:Diarrhea / Q000209:etiology; D004768:Enterotoxins / Q000633:toxicity; D004926:Escherichia coli / Q000472:pathogenicity; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins / Q000633:toxicity; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000502:physiology; D008954:Models, Biological; D009504:Neutrophils / Q000502:physiology; D022621:Shiga Toxin / Q000633:toxicity*; D013927:Thrombosis / Q000209:etiology; D014774:Virulence
D018829:Adhesins, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C066219:enterohemolysin; C034151:heat stable toxin (E coli); D022621:Shiga Toxin