Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/9310
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Platelet endothelial cell adhesion molecule-1 is a negative regulator of platelet-collagen interactions
Author: Jones, K.
Hughan, S.
Dopheide, S.
Farndale, R.
Jackson, S.
Jackson, D.
Citation: Blood, 2001; 98(5):1456-1463
Publisher: Amer Soc Hematology
Issue Date: 2001
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
Karen L. Jones, Sascha C. Hughan, Sacha M. Dopheide, Richard W. Farndale, Shaun P. Jackson, and Denise E. Jackson
Abstract: The functional importance of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in platelets is unclear. Because PECAM-1 represents a newly assigned immunoglobulin-ITIM superfamily member expressed on the surface of platelets, it was hypothesized that it may play an important regulatory role in modulating ITAM-bearing receptors such as collagen (GP)VI receptor and FcgammaRIIA. To examine the functional role of PECAM-1 in regulating platelet-collagen interactions, 2 different approaches were applied using recombinant human PECAM-1-immunoglobulin chimeras and platelets derived from PECAM-1-deficient mice. Stimulation of platelets by collagen-, (GP)VI-selective agonist, collagen-related peptide (CRP)-, and PECAM-1-immunoglobulin chimera induced tyrosine phosphorylation of PECAM-1 in a time- and dose-dependent manner. Activation of PECAM-1 directly through the addition of soluble wild-type PECAM-1-immunoglobulin chimera, but not mutant K89A PECAM-1-immunoglobulin chimera that prevents homophilic binding, was found to inhibit collagen- and CRP-induced platelet aggregation. PECAM-1-deficient platelets displayed enhanced platelet aggregation and secretion responses on stimulation with collagen and CRP, though the response to thrombin was unaffected. Under conditions of flow, human platelet thrombus formation on a collagen matrix was reduced in a dose-dependent manner by human PECAM-1-immunoglobulin chimera. Platelets derived from PECAM-1-deficient mice form larger thrombi when perfused over a collagen matrix under flow at a shear rate of 1800 seconds(-1) compared to wild-type mice. Collectively, these results indicate that PECAM-1 serves as a physiological negative regulator of platelet-collagen interactions that may function to negatively limit growth of platelet thrombi on collagen surfaces.
Keywords: Animals; Mice, Knockout; Humans; Mice; Blood Platelets; Collagen; Serotonin; Peptides; Antigens, CD31; Recombinant Fusion Proteins; Platelet Membrane Glycoproteins; Platelet Adhesiveness; Blood Coagulation; Platelet Aggregation; Rheology; Phosphorylation; Depression, Chemical; Protein Processing, Post-Translational; Infant; Mutagenesis, Site-Directed; Carrier Proteins
Rights: Copyright © 2001 The American Society of Hematology
RMID: 0020011055
DOI: 10.1182/blood.V98.5.1456
Appears in Collections:Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.