title: Rho-GTPase signaling in leukocyte extravasation: an endothelial point of view.
abstract: Leukocyte transendothelial migration (TEM) is one of the crucial steps during inflammation. A better understanding of the key molecules that regulate leukocyte extravasation aids to the development of novel therapeutics for treatment of inflammation-based diseases, such as atherosclerosis and rheumatoid arthritis. The adhesion molecules ICAM-1 and VCAM-1 are known as central mediators of TEM. Clustering of these molecules by their leukocytic integrins initiates the activation of several signaling pathways within the endothelium, including a rise in intracellular Ca (2+), activation of several kinase cascades, and the activation of Rho-GTPases. Activation of Rho-GTPases has been shown to control adhesion molecule clustering and the formation of apical membrane protrusions that embrace adherent leukocytes during TEM. Here, we discuss the potential regulatory mechanisms of leukocyte extravasation from an endothelial point of view, with specific focus on the role of the Rho-GTPases.
authors.affiliation: Department of Molecular Cell Biology; Sanquin Research and Landsteiner Laboratory; Academic Medical Center; University of Amsterdam; Amsterdam, the Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: Heemskerk
authors.affiliation: Department of Molecular Cell Biology; Sanquin Research and Landsteiner Laboratory; Academic Medical Center; University of Amsterdam; Amsterdam, the Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: van Rijssel
authors.affiliation: Department of Molecular Cell Biology; Sanquin Research and Landsteiner Laboratory; Academic Medical Center; University of Amsterdam; Amsterdam, the Netherlands.
authors.forename: Jaap D
authors.initials: JD
authors.lastname: van Buul
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D020741:rho GTP-Binding Proteins
keywords: GTPase; Rho-GEF; diapedesis; extravasation; signaling; transmigration