Lack of mannose-binding lectin-A enhances survival in a mouse model of acute septic peritonitis.
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.
Takahashi
Kazue
K
Department of Pediatrics, Laboratory of Developmental Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. ktakahasi1@partners.org
Gordon
Judith
J
Liu
Hong
H
Sastry
Kedarnath N
KN
Epstein
Judy E
JE
Motwani
Monica
M
Laursen
Inga
I
Thiel
Steffen
S
Jensenius
Jens Christain
JC
Carroll
Michael
M
Ezekowitz
R Alan B
RA
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
D015850:Interleukin-6; D037601:Mannose-Binding Lectin; C445639:Mbl2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C069858:mannose binding protein A