NITRIC-OXIDE - AN ENDOGENOUS MODULATOR OF LEUKOCYTE ADHESION
NITRIC-OXIDE - AN ENDOGENOUS MODULATOR OF LEUKOCYTE ADHESION
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DOI：
10.1073/pnas.88.11.4651
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
GRANGER, DN
中科院分区：
文献类型：
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作者：
KUBES, P;SUZUKI, M;GRANGER, DN
本研究的目的是确定是否内源性一氧化氮（NO）抑制白细胞粘附血管内皮。这是通过用NO产生抑制剂N（G）-单甲基-L-精氨酸（L-NMMA）或N（G）-硝基-L-精氨酸甲酯（L-NAME）灌流猫肠系膜制备物，并通过活体视频显微镜观察单个（直径30 μ m）小静脉来实现的。30分钟的灌流期的粘附和迁移的白细胞，红细胞的速度，和微静脉直径的数量进行了测量;微静脉血流量和剪切速率计算从测量的参数。使用CD 18特异性单克隆抗体IB 4测定白细胞粘附糖蛋白CD 11/CD 18的贡献。这两种抑制剂的NO生产增加白细胞粘附超过15倍。白细胞移出也增强，而小静脉剪切率降低了近一半。抗体IB 4可阻断L-NMMA和L-NAME诱导的白细胞粘附。用L-NMMA而不是L-NAME孵育分离的猫中性粒细胞，通过流式细胞术评估，导致CD 11/CD 18的直接上调。未处理动物的上级肠系膜动脉部分闭塞引起的小静脉剪切率下降表明，L-NAME诱导的白细胞粘附中只有一小部分是剪切率依赖性的。L-精氨酸可抑制L-NAME诱导的粘附，而D-精氨酸则无此作用。这些数据表明，内皮源性NO可能是白细胞粘附的重要内源性调节剂，NO产生的损伤导致白细胞粘附和迁移的模式，这是急性炎症的特征。
The objective of this study was to determine whether endogenous nitric oxide (NO) inhibits leukocyte adhesion to vascular endothelium. This was accomplished by superfusing a cat mesenteric preparation with inhibitors of NO production, N(G)-monomethyl-L-arginine (L-NMMA) or N(G)-nitro-L-arginine methyl ester (L-NAME), and observing single (30-mu-m diameter) venules by intravital video microscopy. Thirty minutes into the superfusion period the number of adherent and emigrated leukocytes, the erythrocyte velocity, and the venular diameter were measured; venular blood flow and shear rate were calculated from the measured parameters. The contribution of the leukocyte adhesion glycoprotein CD11/CD18 was determined using the CD18-specific monoclonal antibody IB4. Both inhibitors of NO production increased leukocyte adherence more than 15-fold. Leukocyte emigration was also enhanced, whereas venular shear rate was reduced by nearly half. Antibody IB4 abolished the leukocyte adhesion induced bby L-NMMA and L-NAME. Incubation of isolated cat neutrophils with L-NMMA, but not L-NAME, resulted in direct upregulation of CD11/CD18 as assessed by flow cytometry. Decrements in venular shear rate induced by partial occlusion of the superior mesenteric artery in untreated animals revealed that only a minor component of L-NAME-induced leukocyte adhesion was shear rate-dependent. The L-NAME-induced adhesion was inhibited by L-arginine but not D-arginine. These data suggest that endothelium-derived NO may be an important endogenous modulator of leukocyte adherence and that impairment of NO production results in a pattern of leukocyte adhesion and emigration that is characteristic of acute inflammation.