title: Minimal regulation of platelet activity by PECAM-1.
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, alphaIIbbeta3, even though both receptors signal through Src-kinase regulation of PLCgamma2. 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 PLCgamma2. 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.
authors: Centre for Cardiovascular Sciences, Institute of Biomedical Research, Division of Medical Sciences, The Medical School, University of Birmingham, Birmingham B15 2TT, UK. t.s.dhanjal@bham.ac.uk
authors: Tarvinder S
authors: TS
authors: Dhanjal
authors: Ewan A
authors: EA
authors: Ross
authors: Jocelyn M
authors: JM
authors: Auger
authors: Owen J T
authors: OJ
authors: McCarty
authors: Craig E
authors: CE
authors: Hughes
authors: Yotis A
authors: YA
authors: Senis
authors: Chris D
authors: CD
authors: Buckley
authors: Steve P
authors: SP
authors: Watson
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D003018:Clot Retraction; D003432:Cross-Linking Reagents / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D005340:Fibrinogen / Q000494:pharmacology; D006801:Humans; D037181:Lectins, C-Type / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051966:Phospholipase C gamma / Q000502:physiology; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000819:agonists / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000097:blood; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: C511991:8-(2,6-dichlorophenyl)-10-methyl-3-((4-morpholin-4-ylphenyl)amino)-2,4,10-triazabicyclo(4.4.0)deca-1,3,5,7-tetraen-9-one; D001372:Aza Compounds; C104778:CLEC2B protein, human; D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D009025:Morpholines; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D047428:Protein Kinase Inhibitors; D014757:Viper Venoms; C435908:collagen-related peptide; C098341:platelet membrane glycoprotein VI; C112292:rhodocytin protein, Calloselasma rhodostoma; D005340:Fibrinogen; D011464:Epoprostenol; D011505:Protein-Tyrosine Kinases; D051966:Phospholipase C gamma; D013917:Thrombin