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PMID: 26584476 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Localized signals that regulate transendothelial migration.

Current opinion in immunology ·Vol. 38 ·2016-02-00 ·Pages 24-9

Muller WA

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.

MeSH Terms
12E7 Antigen Adenylyl Cyclases/genetics,immunology Animals Antigens, CD/genetics,immunology Cadherins/genetics,immunology Calcium/immunology,metabolism Cell Adhesion Molecules/genetics,immunology Cyclic AMP-Dependent Protein Kinases/genetics,immunology Gene Expression Regulation/immunology Humans Leukocytes/cytology,immunology Platelet Endothelial Cell Adhesion Molecule-1/genetics,immunology Signal Transduction/immunology TRPC Cation Channels/genetics,immunology TRPC6 Cation Channel Transendothelial and Transepithelial Migration/immunology
Chemicals
12E7 Antigen Antigens, CD CD99 protein, human Cadherins Cell Adhesion Molecules Platelet Endothelial Cell Adhesion Molecule-1 TRPC Cation Channels TRPC6 Cation Channel TRPC6 protein, human cadherin 5 Cyclic AMP-Dependent Protein Kinases Adenylyl Cyclases Calcium
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Muller William A
Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL 60201, USA. Electronic address: wamuller@northwestern.edu.
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Article Info
Journal
Current opinion in immunology
Abbr.
Curr Opin Immunol
ISSN
1879-0372
DOI
10.1016/j.coi.2015.10.006
Email
wamuller@northwestern.edu
Published
2016-02-00
Epub
2015-00-14
Pages
24-9
Language
English
Region
England
NLM ID
8900118
PMCID
PMC4715928
Subset
IM
Grants
NCI NIH HHS · P30 CA060553 · United States
NHLBI NIH HHS · R01 HL046849 · United States
NHLBI NIH HHS · R01 HL064774 · United States
NHLBI NIH HHS · R37 HL064774 · United States
External Links
PubMed source DOI: 10.1016/j.coi.2015.10.006 PMC Full Text View journal details
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