cAMP signaling in leukocyte transendothelial migration

Magdalena J Lorenowicz, Mar Fernandez-Borja, Peter L Hordijk

Research output: Contribution to journalReview articlepeer-review


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).

Original languageEnglish
Pages (from-to)1014-22
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number5
Publication statusPublished - May 2007
Externally publishedYes


  • Animals
  • Cell Adhesion
  • Cell Movement/physiology
  • Cyclic AMP/metabolism
  • Endothelium, Vascular/metabolism
  • Humans
  • Inflammation/metabolism
  • Leukocytes/metabolism
  • Signal Transduction/physiology


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