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lüll Leukocyte apoptosis and its significance in sepsis and shock Wesche DE; Lomas-Neira JL; Perl M; Chung CS; Ayala AJ Leukoc Biol 2005[Aug]; 78 (2): 325-37Sepsis and multiple organ failure continue to be significant problems among trauma, burn, and the critically ill patient population. Thus, a number 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. Evidence of epithelial as well as endothelial cell apoptotic changes has also been reported. Although mediators such as steroids, tumor necrosis factor, nitric oxide, C5a, and Fas ligand (FasL) appear to contribute 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 molecules (e.g., Bcl-2, Akt) improve survival of septic mice, it not only demonstrates the pathological significance of this process but points to novel targets for the treatment of sepsis.|Animals[MESH]|Apoptosis/*immunology[MESH]|Caspase Inhibitors[MESH]|Caspases/immunology[MESH]|Dendritic Cells/immunology/pathology[MESH]|Endothelial Cells/immunology/pathology[MESH]|Enzyme Inhibitors/therapeutic use[MESH]|Fas Ligand Protein[MESH]|Humans[MESH]|Leukocytes/*immunology/pathology[MESH]|Membrane Glycoproteins/immunology[MESH]|Mice[MESH]|Multiple Organ Failure/drug therapy/immunology/pathology[MESH]|Protein Serine-Threonine Kinases/antagonists & inhibitors/immunology[MESH]|Proto-Oncogene Proteins c-akt[MESH]|Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors[MESH]|Proto-Oncogene Proteins/antagonists & inhibitors/immunology[MESH]|RNA, Small Interfering/immunology/therapeutic use[MESH]|Sepsis/drug therapy/immunology/pathology[MESH]|Shock, Septic/drug therapy/*immunology/pathology[MESH]|Steroids/immunology[MESH]|Tumor Necrosis Factor-alpha/immunology[MESH] |