| Hemorrhagic fever with renal syndrome (HFRS) is a naturally epidemic disease caused by Hantaan virus (HTNV) infection. The principal pathophysiological changes in HFRS include severe fever, hemorrhage and acute renal failure. It was reported that more than 100,000 cases of HFRS occurred annually worldwide with a mortality rate of between 2% and 10%. Among the cases, over 50% of the patients were documented in mainland of China. Unfortunately, however, up to date scientists have not yet found any preventive and therapeutic ways that prove to be effective to HTNV infection.Tumor necrosis factor receptor superfamily (TNFRSF) consisits of a panel of members, among which TNFR-I, Fas and DR4/DR5 are so called death receptors because these receptors have death domain in their cytoplasmic region. Cells expressing TNFR-I, Fas andDR4/DR5 are able to undergo apoptosis when these death receptors are specifically engaged with their counterpart ligands TNF, FasL and TRAIL. Therefore TNF, FasL and TRAIL are named as apoptosis-inducing ligands. More and more studies have indicated that these apoptosis-inducing ligands are essential in clearing viral infected cells. On the other hand, some clues showed that they might be involved in pathological injury of the viral infected or non-infected tissues.Both apoptosis-inducing ligands and death receptors exist physiologically and/or pathologically in the body as membrane bound and soluble forms that behave agonistically or antagonistically to exert complicated immunological modulation. In this thesis, roles of membrane bound and soluble forms of apoptosis-inducing ligands in immune response and pathological injury in the HFRS patients were investigated.Firstly, expression and distribution of membrane bound apoptosis-inducing ligands on different subpopulations (T cells, B cells, monocyte/macrophage and natural killer cells) of PBMC from the HFRS patients were determined by two-color flow cytometry. It was showed that the HFRS patients got much higher ratios of CD3+, CD4+, CD8+ and CD19+populations or subpopulations expressing FasL or TRAIL in PBMC than healthy donors. The percentages of CD3+FasL+, CD4+ FasL+, CD8+FasL+ and CD19+FasL+ subsets in PBMC from the patients were 12.16+4.64%, 2.65+1.08%, 9.62+3.40% and 0.99+0.23% compared with 0.39+0.11%, 0.29+0.08%, 0.12+0.02% and 0.27+0.08% of the healthy donors. The ratios of CD3+TRAIL+, CD4+TRAIL+, CD8+TRAIL+ and CD19+TRAIL+ subsets in PBMC from the patients were 7.23+2.61%,1.25+1.13%, 6.15+2.45% and 2.28+1.4% versus 0.39+0.09%, 0.41+0.28%, 0.30+0.09% and 0.46+0.41% from the healthy donors. Statistical analysis showed that there was no significant increase of FasL and TRAIL expression on the surface of CD144 and CD56+ subsets. Expression of TNF on whole PBMC had nearly no differences between the HFRS patients and healthy donors.Secondly, levels of soluble FasL (sFasL), sTRAIL, sTNF, sIL-2R, IL-6 and IFN-a2a in plasma were quantitatively measured by sandwich ELISAs. 77.69+21.11 pg/ml of TNF, 40.69+6.75 pg/ml of sFasL and 19.04 + 5.54 pg/ml of sTRAIL were detected in plasma from the HFRS patients, which were respectively 4.8-, 6.0-and 1.8-fold of that from the healthy donors (16.26+14.09 pg/ml for TNF, 6.76 +1.01 pg/ml for sFasL, and 10.72 +1.41 pg/ml for sTRAIL). sIL-2R level in plasma from the HFRS patients peaked at febrile phase (1039.32 +81.88 units/ml), and decreased gradually with the progress of illness but still much higher at convalescent phase (326.96+92.58 units/ml) than that in plasma from healthy donors (66.73+6.48 units/ml) (p<0.01). IL-6 level in plasma from the patients (362.46+ 141.26pg/ml) was significantly higher than that from the healthy donors (43.81 + 18.08pg/ml). There was no significant difference between the patients and healthy donors for IFN-a2a level in plasma.Finally, after determination of TNF, FasL and TRAIL expression on different subpopulations of PBMC, the intracellular staining of PBMC for human IFN-y and IL-4 were carried out to determine the ratios of Thl, Th2, Tel, and Tc2 subsets in HFRS p...
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