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© Research
Publication : The Journal of clinical investigation

Integrin-dependent induction of functional urokinase receptors in primary T lymphocytes

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in The Journal of clinical investigation - 01 Sep 1996

Bianchi E, Ferrero E, Fazioli F, Mangili F, Wang J, Bender JR, Blasi F, Pardi R

Link to Pubmed [PMID] – 8787676

J. Clin. Invest. 1996 Sep;98(5):1133-41

In order to reach the sites of inflammation, lymphocytes leave the bloodstream and migrate into peripheral tissues, in a process involving integrin-mediated adhesion to the vascular endothelium, followed by transmigration across the endothelial barrier and through the underlying interstitial matrix. We have investigated the role of the plasminogen activator/plasmin system in normal T cell migration. Receptors for urokinase plasminogen activator (uPAR) were not expressed in resting T lymphocytes, but could be efficiently induced at the mRNA and protein level by coclustering of the antigen receptor complex and beta1 or beta2 integrins, through a signalling pathway involving both protein kinase C activation and an increase in intracellular cyclic AMP. Catalytic activation of plasminogen by uPAR-expressing T cells promoted their migration through an extracellular matrix in vitro. Plasmin-induced invasion was inhibited by plasmin-and urokinase inhibitors and by anti-uPAR antibodies. Finally, cytofluorimetric and immunohistochemical analysis of primary human tumor specimens showed the presence of uPAR positive infiltrating T cells in vivo. Collectively, these findings suggest that plasminogen activation may play a role in lymphocyte migration in vivo, and that integrin-dependent expression of membrane-associated endopeptidases could represent an additional step in the regulated process of leukocyte transmigration.

http://www.ncbi.nlm.nih.gov/pubmed/8787676