Fraticelli A, Serrano C V, Bochner B S, Capogrossi M C, Zweier J L
Molecular and Cellular Biophysics Laboratories and EPR Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA.
Biochim Biophys Acta. 1996 Feb 29;1310(3):251-9. doi: 10.1016/0167-4889(95)00169-7.
While endothelial oxidant generation and subsequent leukocyte chemotaxis and activation are important mechanisms of tissue damage in ischemic organs, it is not known if oxidant generation may be involved in triggering the subsequent leukocyte-mediated injury which occurs. Questions remain whether particular oxidants and oxygen-free radicals are capable of modulating the expression of leukocyte adhesion molecules and effecting leukocyte endothelial adhesion. Studies were performed to determine the effect of different biologically occurring oxidant molecules and oxygen free radicals including: .O2-, .OH, and H2O2 on the expression of integrin and selectin adhesion molecules on the surface of human PMNs and to determine the effect of these alterations on PMN adhesion to the endothelium. Adhesion molecule expression on the surface of human PMNs was measured by immunofluorescence flow cytometry. Electron paramagnetic resonance spectroscopy was applied to characterize the presence of exogenous free radical generation as well as that from activated PMNs. It was observed that these oxidants can cause up-regulation of CD11b and CD18 expression with shedding of L-selectin. The kinetics and dose-response of these effects were analyzed and their functional significance determined by measuring PMN adhesion to cultured human aortic endothelial monolayers. These studies demonstrate that oxygen free radicals and non-radical oxidants can directly trigger PMN activation and adhesion to vascular endothelium.
虽然内皮细胞产生氧化剂以及随后的白细胞趋化和激活是缺血器官组织损伤的重要机制，但尚不清楚氧化剂的产生是否可能参与引发随后发生的白细胞介导的损伤。关于特定的氧化剂和氧自由基是否能够调节白细胞粘附分子的表达并影响白细胞与内皮细胞的粘附，仍然存在疑问。本研究旨在确定不同生物来源的氧化剂分子和氧自由基，包括超氧阴离子（·O₂⁻）、羟自由基（·OH）和过氧化氢（H₂O₂）对人中性粒细胞表面整合素和选择素粘附分子表达的影响，并确定这些变化对中性粒细胞与内皮细胞粘附的影响。通过免疫荧光流式细胞术检测人中性粒细胞表面的粘附分子表达。应用电子顺磁共振光谱法来表征外源性自由基的产生以及活化中性粒细胞产生的自由基。观察到这些氧化剂可导致CD11b和CD18表达上调以及L-选择素脱落。分析了这些效应的动力学和剂量反应，并通过测量中性粒细胞与培养的人主动脉内皮单层的粘附来确定其功能意义。这些研究表明，氧自由基和非自由基氧化剂可直接触发中性粒细胞的激活和与血管内皮的粘附。
