Logo image
Back
Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis
Journal article   Peer reviewed

Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis

Richard S Hotchkiss, Paul E Swanson, C Michael Knudson, Katherine C Chang, J Perren Cobb, Dale F Osborne, Kimberly M Zollner, Timothy G Buchman, Stanley J Korsmeyer and Irene E Karl
The Journal of immunology (1950), Vol.162(7), pp.4148-4156
04/01/1999
DOI: 10.4049/jimmunol.162.7.4148
PMID: 10201940

View Online

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.
 Flow Cytometry In Situ Nick-End Labeling Coloring Agents Apoptosis - genetics Mice, Transgenic Survival Rate Mice, Inbred Strains Proto-Oncogene Proteins c-bcl-2 - biosynthesis Sepsis - mortality Animals Sepsis - pathology Electrophoresis, Agar Gel Hematoxylin Mice Proto-Oncogene Proteins c-bcl-2 - genetics Eosine Yellowish-(YS)

Details

Metrics

20 Record Views
329 Times Cited - Web of Science
Logo image