Over-Expression of Bcl-2 Provides Protection in Septic Mice by a trans Effect

• Published in: The Journal of immunology (1950) Vol. 171; no. 6; pp. 3136 - 3141
• Main Authors: Iwata, Akiko, Stevenson, Vicki Morgan, Minard, Annie, Tasch, Michael, Tupper, Joan, Lagasse, Eric, Weissman, Irving, Harlan, John M, Winn, Robert K
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.09.2003
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.6.3136

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.