title: Lack of mannose-binding lectin-A enhances survival in a mouse model of acute septic peritonitis.
abstract: The mannose-binding lectin (MBL) (also known as the mannose-binding protein) is a serum protein that plays a role as an "ante-antibody" in innate immunity. In man, MBL is encoded by a single gene, whereas in mice there are two homologous proteins, MBL-A and MBL-C. In order to evaluate the relative roles of these two forms of MBL, we created MBL-A null mice that were MBL-C sufficient. We found MBL-A null mice had enhanced survival in a septic peritonitis model compared to wild-type mice and complement 3 null mice at 24 h, 48 h and 10 d (P < 0.05). Reconstitution of these mice with human MBL reversed the phenotype. Surviving mice had significantly decreased TNF-alpha and IL-6 levels in the blood and peritoneal cavity (P < 0.01). In vitro studies indicate that bacteria opsonized with MBL-A-deficient serum induced significantly less cytokine by peritoneal macrophages compared to those with wild-type serum. Our results indicate that MBL-A is a modulator of inflammation in vivo and in vitro in the mouse and that the role of MBL may extend beyond its role as an opsonin.
authors.affiliation: Department of Pediatrics, Laboratory of Developmental Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ktakahasi1@partners.org
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.forename: Judith
authors.initials: J
authors.lastname: Gordon
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Kedarnath N
authors.initials: KN
authors.lastname: Sastry
authors.forename: Judy E
authors.initials: JE
authors.lastname: Epstein
authors.forename: Monica
authors.initials: M
authors.lastname: Motwani
authors.forename: Inga
authors.initials: I
authors.lastname: Laursen
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.forename: Jens Christain
authors.initials: JC
authors.lastname: Jensenius
authors.forename: Michael
authors.initials: M
authors.lastname: Carroll
authors.forename: R Alan B
authors.initials: RA
authors.lastname: Ezekowitz
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017353:Gene Deletion; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis; D007962:Leukocytes / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010538:Peritonitis / Q000235:genetics / Q000276:immunology*; D013234:Stem Cells; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015850:Interleukin-6; D037601:Mannose-Binding Lectin; C445639:Mbl2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C069858:mannose binding protein A