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Real-time Imaging of Endothelial Cell-cell Junctions During Neutrophil Transmigration Under Physiological Flow
Published on: August 14, 2014
cAMP signaling in leukocyte transendothelial migration
Magdalena J Lorenowicz1, Mar Fernandez-Borja, Peter L Hordijk
1Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
Arteriosclerosis, Thrombosis, and Vascular Biology
|March 10, 2007
Summary
Leukocyte migration across blood vessels is vital for immunity and inflammation. This review explores how cyclic AMP (cAMP) signaling, via protein kinase A and Epac, regulates this process and its role in diseases.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Leukocyte transendothelial migration is essential for immune surveillance and inflammatory responses.
- Dysregulated migration contributes to diseases like asthma, rheumatoid arthritis, and atherosclerosis.
- Intracellular messengers, including cyclic AMP (cAMP), regulate leukocyte migration, but cAMP's dual role in promoting and inhibiting inflammation is complex.
Purpose of the Study:
- To review the current understanding of how cAMP-dependent signaling pathways control leukocyte transendothelial migration.
- To highlight the roles of protein kinase A (PKA) and Exchange protein directly activated by cAMP (Epac) as key mediators of cAMP effects.
Main Methods:
- This is a review article, synthesizing existing research on leukocyte migration and cAMP signaling.
- Focuses on molecular mechanisms involving cAMP effectors PKA and Epac.
Main Results:
- cAMP is generated in both leukocytes and endothelial cells, influencing leukocyte chemotaxis and endothelial barrier function.
- Physiological stimuli can lead to both pro- and anti-inflammatory signals mediated by cAMP.
- PKA and Epac are identified as crucial regulators of leukocyte transendothelial migration downstream of cAMP.
Conclusions:
- Understanding cAMP signaling pathways, particularly involving PKA and Epac, is critical for deciphering the complex regulation of leukocyte transendothelial migration.
- Targeting these pathways may offer therapeutic strategies for inflammatory diseases driven by aberrant leukocyte migration.
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