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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1014.)
© 2007 American Heart Association, Inc.

Brief Reviews

cAMP Signaling in Leukocyte Transendothelial Migration

Magdalena J. Lorenowicz; Mar Fernandez-Borja; Peter L. Hordijk

From the Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands.

Correspondence to Peter L. Hordijk, PhD, Sanquin Research and Landsteiner, Laboratory, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands. E-mail p.hordijk{at}sanquin.nl

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).

In this review we discuss the role of cAMP in the control of leukocyte transendothelial migration. Focusing on two major targets of cAMP, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac), we provide an overview of the current knowledge on the regulation of leukocyte transendothelial migration by cAMP-driven signaling in both leukocytes and endothelium.

Key Words: Epac • PKA • migration • leukocytes • endothelial cells

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