Dhanjal, Tarvinder S., Ross, Ewan A., Auger, Jocelyn M., Mccarty, Owen J T, Hughes, Craig E., Senis, Yotis A. and Watson, Steve P. (2007). Minimal regulation of platelet activity by PECAM-1. Platelets, 18 (1), pp. 56-67.
Abstract
PECAM-1 is a member of the superfamily of immunoglobulins (Ig) and is expressed on platelets at moderate level. PECAM-1 has been reported to have contrasting effects on platelet activation by the collagen receptor GPVI and the integrin, αIIbβ3, even though both receptors signal through Src-kinase regulation of PLCγ2. The present study compares the role of PECAM-1 on platelet activation by these two receptors and by the lectin receptor, CLEC-2, which also signals via PLCγ2. Studies using PECAM-1 knockout-mice and cross-linking of PECAM-1 using specific antibodies demonstrated a minor inhibitory role on platelet responses to the above three receptors and also under some conditions to the G-protein agonist thrombin. The degree of inhibition was considerably less than that produced by PGI2, which elevates cAMP. There was no significant difference in thrombus formation on collagen in PECAM-1-/- platelets relative to litter-matched controls. The very weak inhibitory effect of PECAM-1 on platelet activation relative to that of PGI2 indicate that the Ig-receptor is not a major regulator of platelet activation. PECAM-1 has been reported to have contrasting effects on platelet activation. The present study demonstrates a very mild or negligible effect on platelet activation in response to stimulation by a variety of agonists, thereby questioning the physiological role of the immunoglobulin receptor as a major regulator of platelet activation.
| Publication DOI: | https://doi.org/10.1080/09537100600881396 |
|---|---|
| Divisions: | College of Health & Life Sciences College of Health & Life Sciences > School of Biosciences |
| Funding Information: | The synthetic CRP peptide GCP*(GPP*)10GCP*G (where P* denotes a hydroxyproline amino acid residue) was cross-linked through Nand C-terminal cysteine residues as previously described [34, 35]. Fibrillar-type I Horm collagen from equine tendon was from Nycomed (Axis-Shield, UK). Human fibrinogen, depleted of plasminogen, VWF and fibronectin was from Enzyme Research (Swansea, UK). Rhodocytin was kindly provided by Dr Johannes Eble (Muenster, Germany). FcγRIIA specific monoclonal antibody (IV.3) was from Madarex Inc. (Annandale, NJ) and F(ab0)2 fragments were generated using immobilized pepsin according to manufacturer’s instructions. The functional integrity of IV.3 F(ab0)2 fragments was confirmed by their inability to induce FcγRIIA–receptor-mediated platelet activation after crosslinking using a secondary antibody. PECAM-1 knockout-mice were a gift from Dr Tak Mak (Amgen Institute, Toronto, Ontario, Canada). PECAM-1−/− mice were housed under pathogen-free conditions at the University of Birmingham animal SPF facility under National Health and Medical Research Council guidelines and approved animal protocols. PECAM-1−/− mice were bred from heterozygotes on a C57Bl6 background. The phenotype of the PECAM-1−/− was confirmed by flow cytometric analysis of leukocytes [21]. Anti-human PECAM1.3 IgG1 mAb was a gift from Prof. Peter Newman (Blood Research Institute, Milwaukee, WI, USA). PECAM-1 mAb AB468 was from Autogen-Bioclear (Wiltshire, UK). Sheep anti-mouse IgG F(ab’)2 fragments, a mouse IgG1 isotype control and bovine plasma thrombin were purchased from Sigma (Poole, UK). mAb AB468 and control IgG1 were dialysed prior to experimentation to remove azide. PD0173952 was a gift from Pfizer Global Research & Development (Ann Arbor, MI, USA and Sandwich, UK). This work was funded by the British Heart Foundation. We would like to thank Peter Newman for supplying the PECAM-1.3 antibody and Pfizer Global Research & Development for supplying PD0173952. |
| Additional Information: | This is an Accepted Manuscript of an article published by Taylor & Francis Group in Platelets on Feb 2007, available online at: http://10.1080/09537100600881396 |
| Uncontrolled Keywords: | CLEC-2,GPVI,Integrin αβ,PECAM-1,Platelet activation,Hematology,Cell Biology |
| Publication ISSN: | 1369-1635 |
| Last Modified: | 10 Mar 2026 08:05 |
| Date Deposited: | 09 Sep 2019 10:05 |
| Full Text Link: | |
| Related URLs: |
https://www.sco ... ons/33847039218
(Scopus URL) |
PURE Output Type: | Article |
| Published Date: | 2007-02-01 |
| Authors: |
Dhanjal, Tarvinder S.
Ross, Ewan A. ( 
0000-0001-5733-9361)
Auger, Jocelyn M. Mccarty, Owen J T Hughes, Craig E. Senis, Yotis A. Watson, Steve P. |