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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83 Citations (Scopus)

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.
Original languageEnglish
JournalMicrobes and Infection
Volume4
Issue8
Pages (from-to)773-84
Number of pages12
ISSN1286-4579
Publication statusPublished - 2002

Keywords

  • Animals
  • Disease Models, Animal
  • Gene Deletion
  • Inflammation
  • Interleukin-6
  • Leukocytes
  • Mannose-Binding Lectin
  • Mice
  • Mice, Knockout
  • Peritonitis
  • Stem Cells
  • Survival Analysis
  • Tumor Necrosis Factor-alpha

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