Lorenowicz Magdalena J, Fernandez-Borja Mar, Hordijk Peter L
Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
Arterioscler Thromb Vasc Biol. 2007 May;27(5):1014-22. doi: 10.1161/ATVBAHA.106.132282. Epub 2007 Mar 8.
The migration of leukocytes across the vascular endothelium is crucial for immunosurveillance as well as for inflammatory responses. Uncontrolled leukocyte transendothelial migration results in pathologies such as asthma, rheumatoid arthritis, and atherosclerosis. The molecular mechanisms that regulate leukocyte transendothelial migration involve signaling downstream of intracellular messengers such as cAMP, calcium, phosphoinositol lipids, or reactive oxygen species. Among these, cAMP is particularly intriguing because it is generated in both leukocytes and endothelial cells and regulates leukocyte chemotaxis as well as endothelial barrier function. In addition, physiological stimuli that induce cAMP production generate both pro- and antiinflammatory signals, underscoring the complexity of cAMP-driven signaling. This review discusses our current knowledge of the control of leukocyte transendothelial migration by two main cAMP effectors: protein kinase A and the Rap exchange factor Epac (Exchange protein directly activated by cAMP).
白细胞穿越血管内皮的迁移对于免疫监视以及炎症反应至关重要。不受控制的白细胞跨内皮迁移会导致诸如哮喘、类风湿性关节炎和动脉粥样硬化等病症。调节白细胞跨内皮迁移的分子机制涉及细胞内信使（如cAMP、钙、磷酸肌醇脂质或活性氧）下游的信号传导。其中，cAMP特别引人关注，因为它在白细胞和内皮细胞中均有生成，并调节白细胞趋化性以及内皮屏障功能。此外，诱导cAMP产生的生理刺激会产生促炎和抗炎信号，突出了cAMP驱动信号传导的复杂性。本综述讨论了我们目前对两种主要cAMP效应器（蛋白激酶A和Rap交换因子Epac，即直接由cAMP激活的交换蛋白）控制白细胞跨内皮迁移的了解。
