globotriaosylceramide and Purpura--Thrombotic-Thrombocytopenic

Hemolytic uremic syndrome (HUS) is caused by endothelial cell damages. Ninety percent of children with HUS have verotoxin-producing E.coli infection. Verotoxin binds to glycolipid receptors globotriaosyl ceramide (Gb3), and the difference of Gb3 expression level in each organ would lead to specific organ involvement. The receptors are expressed in human renal cortex and medulla. The expression level of Gb3 in normal human brain has not been characterized completely. However involvement of central nervous system is a severe complication of HUS. Spreading of microvascular thrombosis caused by combined effects of lipopolysaccharide, cytokine, enhanced shear stress, and verotoxin would play a major role in the development of central nervous dysfunction.

Topics: Bacterial Toxins; Central Nervous System Diseases; Escherichia coli Infections; Escherichia coli O157; Gastrointestinal Hemorrhage; Hemolytic-Uremic Syndrome; Humans; Purpura, Thrombotic Thrombocytopenic; Shiga Toxin 1; Trihexosylceramides

Oral infection with enterohemorrhagic Escherichia coli (EHEC) may cause severe enteritis, followed in up to 10% of cases by an extraintestinal complication, the hemolytic uremic syndrome (HUS). HUS is characterized by a triad of symptoms: anemia, thrombocytopenia, and acute renalfailure due to thrombotic microangiopathy. EHEC produces several virulence factors, among which a family of phage-encoded cytotoxins, called Shiga toxin 1 and Shiga toxin 2, seems to be most important. However, since an appropriate animal model is not available, pathogenicity of these emerging enteric pathogens is still poorly understood. Germ-free gnotobiotic piglets infected orally with an O1577:H7 or an O26:H11 EHEC wild-type isolate, both producing Shiga toxin 2, developed intestinal and extraintestinal manifestations of EHEC disease, including thrombotic microangiopathy in the kidneys, the morphologic hallmark of HUS in humans. Thus, gnotobiotic piglets are suitable to further study the pathophysiology of EHEC-induced HUS. It can be expected that data obtainedfrom this animal model will improve our current standard of knowledge about this emerging infectious disease.

Topics: Animals; Child, Preschool; Digestive System; Disease Models, Animal; Endothelium, Vascular; Escherichia coli Infections; Escherichia coli O157; Female; Germ-Free Life; Hemolytic-Uremic Syndrome; Humans; Immunohistochemistry; Kidney; Microcirculation; Purpura, Thrombotic Thrombocytopenic; Shiga Toxin 2; Swine; Swine Diseases; Trihexosylceramides