Over-Expression of Bcl-2 Provides Protection in Septic Mice by a trans Effect
| Autor: | Annie Minard, John M. Harlan, Michael Tasch, Vicki Morgan Stevenson, Robert K. Winn, Eric Lagasse, Irving L. Weissman, Joan C. Tupper, Akiko Iwata |
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| Rok vydání: | 2003 |
| Předmět: |
Genetically modified mouse
Adoptive cell transfer T-Lymphocytes Transgene Immunology Colony Count Microbial Apoptosis Mice Transgenic Punctures Biology Leukocyte Count Mice Cecum Peritoneum Sepsis medicine Animals Ascitic Fluid Humans Immunology and Allergy Myeloid Cells Peritoneal Lavage Intestinal Mucosa Ligation Survival analysis Bone Marrow Transplantation Homeodomain Proteins Mice Knockout CD11b Antigen medicine.disease Adoptive Transfer Survival Analysis Molecular biology Mice Inbred C57BL medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 B-cell leukemia Cytokines Bone marrow |
| Zdroj: | The Journal of Immunology. 171:3136-3141 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.171.6.3136 |
| Popis: | 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 Eμ promoter (Eμ-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 Eμ-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. |
| Databáze: | OpenAIRE |
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