The role of programmed cell death (apoptosis) in thymic involution following sepsis

Autor: Rebecca B. Chapin, Sabita Roy, Roderick A. Barke, Richard Charboneau
Rok vydání: 1994
Předmět:
Zdroj: Archives of surgery (Chicago, Ill. : 1960). 129(12)
ISSN: 0004-0010
Popis: Objective: To test the hypothesis that thymic involution following peritoneal sepsis is secondary to thymocyte programmed cell death. Design: We investigated the temporal response of thymic weight and thymic DNA fragmentation following peritoneal sepsis induced by cecal ligation and puncture in a rat model. We investigated the possible role of decreased interleukin (IL)-2 synthesis in the induction of apoptosis using rat thymocytes in primary culture. Finally, we studied IL-2 gene expression and IL-2 protein synthesis in phytohemagglutinin and IL-1β–treated thymocytes derived from the cecal ligation and puncture model of sepsis. Results: We demonstrated that (1) there is a significant decrease in thymic weight and an increase in thymic DNA fragmentation with the characteristic apoptotic DNA "ladder" fragmentation pattern on agarose gel electrophoresis following peritoneal sepsis; (2) thymocytes in primary culture sustain a significant increase in thymocyte apoptosis following IL-2 withdrawal; and (3) peritoneal sepsis results in inhibition of phytohemagglutinin and IL-1β–induced thymocyte IL-2 messenger RNA accumulation and protein synthesis. Conclusions: Thymic involution following peritoneal sepsis is associated with increased thymocyte programmed cell death. Thymocyte apoptosis induced by sepsis may be the result, in part, of inhibition of IL-2 gene expression. (Arch Surg. 1994;129:1256-1262)
Databáze: OpenAIRE