Leukocyte apoptosis and its significance in sepsis and shock

Abstract: Sepsis and multiple organ failure con-tinue to be significant problems among trauma, burn, and the critically ill patient population. Thus, a num-ber of laboratories have focused on understanding the role of altered apoptotic cell death in contributing to immune and organ dysfunction seen in sepsis and shock. Immune cells that undergo altered apoptotic changes include neutrophils, macrophages, dendritic cells, as well as various lymphocyte populations. Ev-idence of epithelial as well as endothelial cell apopto-tic changes has also been reported. Although media-tors such as steroids, tumor necrosis factor, nitric oxide, C5a, and Fas ligand (FasL) appear to contrib-ute to the apoptotic changes, their effects are tissue-and cell population-selective. As inhibiting Fas-FasL signaling (e.g., gene deficiency, Fas fusion protein, or Fas short interfering RNA administration), caspase inhibition (caspase mimetic peptides), and/or the overexpression of downstream antiapoptotic mole-cules (e.g., Bcl-2, Akt) improve survival of septic mice, it not only demonstrates the pathological sig-nificance of this process but points to novel targets for the treatment of sepsis. J. Leukoc. Biol. 78