title: LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system.
abstract: Intravenous injection of a lipopolysaccharide (LPS) into mice induces a rapid accumulation of platelets in the lung and liver. When degradation of the accumulated platelets occurs, anaphylactoid shock follows rapidly, the severity of the shock paralleling the quantity of platelets accumulated in the lung. Here we examined the contributions made by LPS structure and the complement system to the platelet response to LPS. BALB/c mice were injected with an LPS from Escherichia coli O8, O9, O111, or K-12, or from recombinant mutants of K-12. The O-regions of the O8 and O9 LPSs consist of a mannose homopolysaccharide (MHP), while that of O111 consists of a heteropolysaccharide (not including mannose), and K-12 LPS lacks an O-region. O111 LPS was devoid of the ability to induce the platelet response or shock, while the ability of K-12 LPS was weak. The 2 recombinant LPSs-each having an O-region (from O8 or O9) linked to K-12 LPS-exhibited activities similar to or stronger than those of their original LPSs. Mannose-binding lectin (MBL) complexed with MBL-associated serine proteases (MASPs) bound strongly to LPSs containing MHP and caused C4 activation. Moreover, the abilities of these LPSs to activate the complement system corresponded well with their abilities to induce the platelet response and rapid shock. These results suggest that the structure of the O-antigen region is important for the platelet response to LPS, and that activation of the lectin pathway of the complement system is involved in this response.
authors.affiliation: Departments of Oral Microbiology, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhao
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ohtaki
authors.forename: Kouji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Misao
authors.initials: M
authors.lastname: Matsushita
authors.forename: Teizo
authors.initials: T
authors.lastname: Fujita
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Takada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000707:Anaphylaxis / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D003167:Complement Activation / Q000187:drug effects*; D003181:Complement C4 / Q000378:metabolism; D003182:Complement C5 / Q000037:antagonists & inhibitors; D004731:Endotoxins / Q000737:chemistry / Q000633:toxicity*; D004926:Escherichia coli / Q000737:chemistry; D006632:Histamine / Q000097:blood; D006801:Humans; D007275:Injections, Intravenous; D037102:Lectins; D008070:Lipopolysaccharides / Q000737:chemistry / Q000633:toxicity*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D008358:Mannose / Q000032:analysis; D037601:Mannose-Binding Lectin / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D019081:O Antigens / Q000737:chemistry / Q000633:toxicity*; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D011738:Pyrilamine / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism; D012701:Serotonin / Q000097:blood; D012717:Sesquiterpenes / Q000494:pharmacology; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced*; D013329:Structure-Activity Relationship
chemical_list: D003181:Complement C4; D003182:Complement C5; D004731:Endotoxins; C114999:K-12 lipopolysaccharide; C043237:Klebsiella O3 lipopolysaccharide; D037102:Lectins; D008070:Lipopolysaccharides; D037601:Mannose-Binding Lectin; D019081:O Antigens; D012717:Sesquiterpenes; D012701:Serotonin; C044101:endotoxin, Escherichia coli; C038797:K 76 carboxylic acid; D006632:Histamine; D010047:Ovalbumin; C468572:MASP-3 protein, mouse; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases; D011738:Pyrilamine; D008358:Mannose