title: Localized signals that regulate transendothelial migration.
abstract: Transendothelial migration (TEM) of leukocytes is the step in leukocyte emigration in which the leukocyte actually leaves the blood vessel to carry out its role in the inflammatory response. It is therefore, arguably the most critical step in emigration. This review focuses on two of the many aspects of this process that have seen important recent developments. The adhesion molecules, PECAM (CD31) and CD99 that regulate two major steps in TEM, do so by regulating specific signals. PECAM initiates the signaling pathway responsible for the calcium flux that is required for TEM. Calcium enters through the cation channel TRPC6 and recruits the first wave of trafficking of membrane from the lateral border recycling compartment (LBRC). CD99 signals through soluble adenylate cyclase to activate protein kinase A to recruit a second wave of LBRC trafficking. Another process that is critical for TEM is transient removal of VE-cadherin from the site of TEM. However, the local signaling pathways that are responsible for this appear to be different from those that open the junctions to increase vascular permeability.
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60201, USA. Electronic address: wamuller@northwestern.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Muller
mesh_terms: D000071443:12E7 Antigen; D000262:Adenylyl Cyclases / Q000235:genetics / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015820:Cadherins / Q000235:genetics / Q000276:immunology; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000276:immunology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D050052:TRPC Cation Channels / Q000235:genetics / Q000276:immunology; D000074287:TRPC6 Cation Channel; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology*; D000099152:Cadherin 5
chemical_list: D000071443:12E7 Antigen; D000262:Adenylyl Cyclases; D015703:Antigens, CD; D015820:Cadherins; D002118:Calcium; D015815:Cell Adhesion Molecules; D017868:Cyclic AMP-Dependent Protein Kinases; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; D000099152:Cadherin 5; C061828:CD99 protein, human; C117032:TRPC6 protein, human