Is Fas ligand or endotoxin responsible for mucosal lymphocyte apoptosis in sepsis?

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BACKGROUND: (Ao) is a normal constitutive process that seems to have pathological effects in diseases of and , as well as in certain lymphoid tissues during . Little is known about this process in mucosal lymphoid tissue, such as intestinal intraepithelial lymphocytes (IELs).: To determine whether induces increased Ao in small intestinal IEL, whether this was associated with functional changes in cytokine gene expression in the IEL, and which mediators control this process and their impact on the survival of the with .: Male C3H/HeN (endotoxin-sensitive), C3H/HeJ (endotoxin-tolerant), and C3H/HeJ-FasLgld (endotoxin-tolerant/[FasL]-deficient) were subjected to (cecal ligation and puncture []) and IELs were harvested at 4 (early) or 24 hours (late ). Alterations in the cell phenotype and Ao (TUNEL [terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-nick-end labeling] assay) were determined by 3-color flow cytometry. Cytokine gene expression was assessed by multiprobe RNase protection assay.: At 4 hours after , only the frequency of IEL which was CD8+ decreased markedly. By 24 hours after , the number of CD8+ and + cells decreased while the proportion of double-negative cells showed a marked increase when compared with sham-controls. The percentage of Ao positive in CD8+ and + double-positive and double-negative cells increased markedly 24 hours after concomitant with a significant (P<.05 vs sham-controls, Mann-Whitney U test) increase in expression of the , , and gene. These data collectively suggest that causes -induced Ao that may be mediated by FasL. Additional studies were done to determine if the increased Ao was due to either endotoxin or FasL. The results of studies with endotoxin-tolerant C3H/HeJ or FasL-deficient C3H/HeJ-FasLgld showed an increase in A,, in + and CD8+ cells from septic C3H/HeJ but not C3H/HeJ-FasLgld . With regard to septic mortality, our results indicated that there was a marked reduction in mortality in C3H/HeJ-FasLgld vs C3H/HeJ .: We conclude that the phenotypic changes associated with increased Ao may be a reflection of localized due to a FasL-mediated process and not endotoxin. Thus, FasL directly and/or indirectly contributes to higher septic mortality.

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Animals Mice, Inbred C3H Mice Lymphoid Tissue Intestinal Mucosa Sepsis Disease Models, Animal Antigens, CD95 Survival Rate Endotoxins