Role of superoxide in hemorrhagic shock-induced P-selectin expression
Role of superoxide in hemorrhagic shock-induced P-selectin expression
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DOI：
10.1152/ajpheart.2000.279.2.h791
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发表时间：
2000-08-01
影响因子：
4.8
通讯作者：
Granger, DN
中科院分区：
文献类型：
--
作者：
Akgür, FM;Brown, MF;Granger, DN
在不同的炎症实验模型中，超氧化物参与了内皮细胞粘附分子表达的调节和随后白细胞-内皮细胞粘附的启动。本研究的目的是评估氧自由基对全身缺血-再灌注小鼠模型中P-选择素表达的贡献，即，出血复苏（H/R），使用不同的策略干扰氧自由基的产生（别嘌呤醇、CD 11/CD 18缺陷或p47（phox）-/-小鼠）或积累[静脉内超氧化物歧化酶（SOD），过表达SOD的突变小鼠]。P-选择素的表达定量在不同区域的血管床通过使用双放射性标记的单克隆抗体技术。H/R引起所有血管床中P-选择素表达的显著增加。这种反应在SOD转基因小鼠和野生型小鼠接受静脉内SOD或黄嘌呤氧化酶抑制剂别嘌呤醇钝化。在NADPH氧化酶或白细胞粘附分子CD 11/CD 18的亚基中遗传缺陷的小鼠也表现出减少的P-选择素表达。这些结果牵连超氧化物，来自黄嘌呤氧化酶和NADPH氧化酶，作为介质的P-选择素的表达增加，观察到在不同的区域血管床暴露于出血和输血。
Superoxide has been implicated in the regulation of endothelial cell adhesion molecule expression and the subsequent initiation of leukocyte-endothelial cell adhesion in different experimental models of inflammation. The objective of this study was to assess the contribution of oxygen radicals to P-selectin expression in a murine model of whole body ischemia-reperfusion, i.e., hemorrhage-resuscitation (H/R), with the use of different strategies that interfere with either the production (allopurinol, CD11/CD18-deficient or p47(phox)-/- mice) or accumulation [intravenous superoxide dismutase (SOD), mutant mice that overexpress SOD] of oxygen radicals. P-selectin expression was quantified in different regional vascular beds by use of the dual-radiolabeled monoclonal antibody technique. H/R elicited a significant increase in P-selectin expression in all vascular beds. This response was blunted in SOD transgenic mice and in wild-type mice receiving either intravenous SOD or the xanthine oxidase inhibitor allopurinol. Mice genetically deficient in either a subunit of NADPH oxidase or the leukocyte adhesion molecule CD11/CD18 also exhibited a reduced P-selectin expression. These results implicate superoxide, derived from both xanthine oxidase and NADPH oxidase, as mediators of the increased P-selectin expression observed in different regional vascular beds exposed to hemorrhage and retransfusion.