title: Complement activation on platelet-leukocyte complexes and microparticles in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome.
abstract: Hemolytic uremic syndrome (HUS) is commonly associated with Shiga toxin (Stx)-producing Escherichia coli O157:H7 infection. This study examined patient samples for complement activation on leukocyte-platelet complexes and microparticles, as well as donor samples for Stx and lipopolysaccharide (O157LPS)-induced complement activation on platelet-leukocyte complexes and microparticles. Results, analyzed by flow cytometry, showed that whole blood from a child with HUS had surface-bound C3 on 30% of platelet-monocyte complexes compared with 14% after recovery and 12% in pediatric controls. Plasma samples from 12 HUS patients were analyzed for the presence of microparticles derived from platelets, monocytes, and neutrophils. Acute-phase samples exhibited high levels of platelet microparticles and, to a lesser extent, monocyte microparticles, both bearing C3 and C9. Levels decreased significantly at recovery. Stx or O157LPS incubated with donor whole blood increased the population of platelet-monocyte and platelet-neutrophil complexes with surface-bound C3 and C9, an effect enhanced by costimulation with Stx and O157LPS. Both Stx and O157LPS induced the release of C3- and C9-bearing microparticles from platelets and monocytes. Released microparticles were phagocytosed by neutrophils. The presence of complement on platelet-leukocyte complexes and microparticles derived from these cells suggests a role in the inflammatory and thrombogenic events that occur during HUS.
authors: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors: Anne-lie
authors: AL
authors: Ståhl
authors: Lisa
authors: L
authors: Sartz
authors: Diana
authors: D
authors: Karpman
mesh_terms: D001792:Blood Platelets / Q000276:immunology; D055252:Cell-Derived Microparticles / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation / Q000187:drug effects; D003176:Complement C3 / Q000378:metabolism; D015926:Complement C3a / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000187:drug effects; D004927:Escherichia coli Infections / Q000097:blood* / Q000276:immunology*; D019453:Escherichia coli O157; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D022622:Shiga Toxin 1 / Q000633:toxicity; D022641:Shiga Toxin 2 / Q000633:toxicity
chemical_list: D003176:Complement C3; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D008070:Lipopolysaccharides; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a