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The role and regulation of apoptosis in sepsis

Division of Surgical Research, Department of Surgery, RI Hospital/Brown University School of Medicine, Providence, Rhode Island, USA

Joanne L. Lomas-Neira

Division of Surgical Research, Department of Surgery, RI Hospital/Brown University School of Medicine, Providence, Rhode Island, USA

Mario Perl

Division of Surgical Research, Department of Surgery, RI Hospital/Brown University School of Medicine, Providence, Rhode Island, USA

Leslie Jones

Division of Surgical Research, Department of Surgery, RI Hospital/Brown University School of Medicine, Providence, Rhode Island, USA

Chun-Shiang Chung

Division of Surgical Research, Department of Surgery, RI Hospital/Brown University School of Medicine, Providence, Rhode Island, USA

Alfred Ayala

Division of Surgical Research, Department of Surgery, RI Hospital/Brown University School of Medicine, Providence, Rhode Island, USA, aayala{at}lifespan.org

Today, sepsis continues to be a growing problem in the critically ill patient population. A number of laboratories have been interested in understanding how changes in immune cell apoptosis during sepsis appear to contribute to septic morbidity. Consistently, it has been found that immune cell apoptosis is altered in a variety of tissue sites and cell populations both in experimental animals and humans. While divergent mediators, such as steroids and TNF, contribute to some of these apoptotic changes, their effects are tissue and cell population selective. Inhibition of FasL—Fas signaling (by either FasL gene deficiency, in vivo gene silencing [siRNA] or with FasL binding protein) protects septic mice from the onset of marked apoptosis and the morbidity/mortality seen in sepsis. Further, this extrinsic apoptosis response appears to utilize aspects of the Bid-induced mitochondrial pathway. This is in keeping with the findings that pan-specific caspase inhibition or the overexpression of Bcl-2 also protect these animals from the sequellae of sepsis.

Key Words: Sepsis • mice • human • death-receptor pathway • mitochondrial pathway • immune and organ dysfunction

Journal of Endotoxin Research, Vol. 11, No. 6, 375-382 (2005)
DOI: 10.1177/09680519050110060101


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