Lack of mannose-binding lectin-A enhances survival in a mouse model of acute septic peritonitis

Kazue Takahashi, Judith Gordon, Hong Liu, Kedarnath N Sastry, Judy E Epstein, Monica Motwani, Inga Laursen, Steffen Thiel, Jens Christian Jensenius, Michael Carroll, R Alan B Ezekowitz

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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.
OriginalsprogEngelsk
TidsskriftMicrobes and Infection
Vol/bind4
Nummer8
Sider (fra-til)773-84
Antal sider12
ISSN1286-4579
StatusUdgivet - 2002

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