Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 14, Issue -, Pages 2522-2545Publisher
BIOSCIENCE RESEARCH INST-BRI
DOI: 10.2741/3395
Keywords
Endothelial cell; Transendothelial migration; Paracellular; Transcellular; Reactive oxygen species; GTPase; Cytoskeleton; Cell junctions; Transmigratory cup structures; Podosomes; Review
Categories
Funding
- National Institutes of Health [HL-080166, HL-45100]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL080166, P01HL045100] Funding Source: NIH RePORTER
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As the primary physical barrier between blood and tissue compartments within the body, blood vessel endothelial cells and integrity of the cell junctions connecting them must be carefully regulated to support leukocyte transendothelial migration only when necessary. Leukocytes utilize two independent routes across the endothelium: the paracellular route involves migration in between adjacent endothelial cells and requires the transient disassembly of endothelial cell junctions, while the transcellular route occurs directly through an individual endothelial cell, likely requiring the formation of a channel or pore. In this review, I will first summarize the signaling events that are transduced by leukocyte engagement of endothelial cell-surface receptors like ICAM-1 and VCAM-1. Some of these signals include activation of GTPases, production of reactive oxygen species, and phosphorylation of target proteins. These signaling pathways converge to cause junctional disruption, cytoskeletal remodeling, and/or the membrane fusion events that are associated with leukocyte transendothelial migration. The review will conclude with a detailed discussion of the newly characterized transmigratory cup structure, and the recent advances made towards understanding the mechanisms of transcellular transendothelial migration.
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