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Thromb Haemost 2006; 95(05): 873-880
DOI: 10.1160/TH05-12-0812
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Cleavage of human 7-domain VCAM-1 (CD106) by thrombin

Steven R. Barthel
1   Departments of Biomolecular Chemistry
2   Medicine, University of Wisconsin, Madison, Wisconsin, USA
,
Mats W. Johansson
2   Medicine, University of Wisconsin, Madison, Wisconsin, USA
,
Douglas S. Annis
2   Medicine, University of Wisconsin, Madison, Wisconsin, USA
,
Deane F. Mosher
1   Departments of Biomolecular Chemistry
2   Medicine, University of Wisconsin, Madison, Wisconsin, USA
› Author AffiliationsFinancial support: This study was supported by Specialized Center of Research (SCOR) grant HL56396 and Hematology Training grant RTH T32 HL007899 and General Clinical Research Center (GCRC) grant M01 RR03186 from the National Institutes of Health.
Further Information

Publication History

Received 21 December 2005

Accepted after revision 02 March 2006

Publication Date:
01 December 2017 (online)

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Summary

Vascular cell adhesion molecule 1 (VCAM-1,CD106) is expressed as a type I transmembrane integrin counter-receptor on activated endothelium and mediates white blood cell attachment. The alternatively spliced 7-domain (7d) form of VCAM-1 contains a potential thrombin cleavage site. Thrombin proteolysis of 7d-VCAM-1 may help regulate adhesive activity of VCAM-1. We determined whether 7d-VCAM-1 is proteolyzed and rendered inactive by thrombin. Recombinant extracellular domain of 7d-VCAM-1 was cleaved by thrombin to generate 33- and 44-kDa products. Cleavage was in the sequence PGPR/IAAQIG near the N-terminal border of the alternatively spliced fourth immunoglobulin (Ig)-like module. There was no cleavage of 6d-VCAM-1 lacking the fourth module. Expression of full-length 7d-VCAM-1 presented on Chinese hamster ovary (CHO) monolayers, as detected by flow cytometry with an antibody directed to Ig-like modules 1–3, was reduced by thrombin treatment whereas there was no reduction in the expression of fulllength 6d-VCAM-1. Adhesion of blood eosinophils to full-length 7d-VCAM-1 was reduced after treatment of CHO cells with thrombin, whereas adhesion to full-length 6d-VCAM-1 was not affected. We conclude that cleavage of 7d-VCAM-1 by thrombin is a potential mechanism for differential regulation of VCAM-1 splice forms in white blood cell adhesion and trafficking.

Keywords

Adhesion molecules - adhesion receptors/integrins - leukocyte function/activation - leukocyte trafficking/recruitment - thrombin
 

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