Over-expression of Bcl-2 provides protection in septic mice by a trans effect

J Immunol. 2003 Sep 15;171(6):3136-41. doi: 10.4049/jimmunol.171.6.3136.

Abstract

Transgenic mice that over-express B cell leukemia/lymphomas (Bcl)-2 in myeloid cells under control of the human MRP8 promoter (hMRP8-Bcl-2) or in T lymphocytes under the E micro promoter (E micro -Bcl-2) were compared with C57BL/6 control mice following cecal ligation and puncture (CLP). There was a significant difference in outcome between the hMRP8-Bcl-2 and control mice with 100% survival in the hMRP8-Bcl-2 mice vs 25% survival in the control mice. In separate experiments there was a significant difference between E micro -Bcl-2 and control mice with 87.5 and 22.2% survival, respectively. Adoptive transfer of CD11b-positive bone marrow cells from hMRP8-Bcl-2 or C57BL/6 mice to C57BL/6 mice subjected to CLP resulted in 100 and 0% survival, respectively. Adoptive transfer of CD11b-positive cells from either hMRP8-Bcl-2 or C57BL/6 mice to Rag-1(-/-) mice (no mature T or B cells) subjected to CLP resulted in survival of 87.5 and 12.5%, respectively. The hMRP8-Bcl-2 mice had significantly more neutrophils and fewer bacteria in the peritoneum compared with C57BL/6 mice 24 h after CLP. These experiments show that Bcl-2 over-expression is protective in CLP and that protection is independent of lymphocytes. We propose that over-expression of Bcl-2 in T cells or myeloid cells induce release of a molecule(s) that protects against death following CLP.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Apoptosis / genetics
  • Ascitic Fluid / genetics
  • Ascitic Fluid / microbiology
  • Ascitic Fluid / pathology
  • Ascitic Fluid / prevention & control
  • Bone Marrow Transplantation / immunology
  • CD11b Antigen / biosynthesis
  • Cecum
  • Colony Count, Microbial
  • Cytokines / analysis
  • Homeodomain Proteins / genetics
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Leukocyte Count
  • Ligation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Cells / metabolism
  • Peritoneal Lavage
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Punctures
  • Sepsis / genetics*
  • Sepsis / microbiology
  • Sepsis / pathology
  • Sepsis / prevention & control*
  • Survival Analysis
  • T-Lymphocytes / metabolism

Substances

  • CD11b Antigen
  • Cytokines
  • Homeodomain Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RAG-1 protein