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Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1999 Apr 01; Vol. 162 (7), pp. 4148-56. - Publication Year :
- 1999
-
Abstract
- In sepsis there is extensive apoptosis of lymphocytes, which may be beneficial by down-regulating the accompanying inflammation. Alternatively, apoptosis may be detrimental by impairing host defense. We studied whether Bcl-2, a potent antiapoptotic protein, could prevent lymphocyte apoptosis in a clinically relevant model of sepsis. Transgenic mice in which Bcl-2 was overexpressed in T cells had complete protection against sepsis-induced T lymphocyte apoptosis in thymus and spleen. Surprisingly, there was also a decrease in splenic B cell apoptosis in septic Bcl-2 overexpressors compared with septic HeJ and HeOuJ mice. There were marked increases in TNF-alpha, IL-1beta, and IL-10 in thymic tissue in sepsis in the three species of mice, and the increase in TNF-alpha and IL-10 in HeOuJ mice was greater than that in Bcl-2 mice. Mitotracker, a mitochondrial membrane potential indicator, demonstrated a sepsis-induced loss of membrane potential in T cells in HeJ and HeOuJ mice but not in Bcl-2 mice. Importantly, Bcl-2 overexpressors also had improved survival in sepsis. To investigate the potential impact of loss of lymphocytes on survival in sepsis, Rag-1-/- mice, which are totally deficient in mature T and B cells, were also studied. Rag-1-/- mice had decreased survival compared with immunologically normal mice with sepsis. We conclude that overexpression of Bcl-2 provides protection against cell death in sepsis. Lymphocyte death may be detrimental in sepsis by compromising host defense.
- Subjects :
- Animals
Coloring Agents
Electrophoresis, Agar Gel
Eosine Yellowish-(YS)
Flow Cytometry
Hematoxylin
In Situ Nick-End Labeling
Mice
Mice, Inbred Strains
Mice, Transgenic
Survival Rate
Apoptosis genetics
Proto-Oncogene Proteins c-bcl-2 biosynthesis
Proto-Oncogene Proteins c-bcl-2 genetics
Sepsis mortality
Sepsis pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 162
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 10201940