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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aza Compounds / pharmacology
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Carrier Proteins / pharmacology
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Clot Retraction
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Cross-Linking Reagents / pharmacology
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Epoprostenol / pharmacology
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Female
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Fibrinogen / pharmacology
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Humans
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Lectins, C-Type / physiology
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Male
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Morpholines / pharmacology
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Peptides / pharmacology
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Phospholipase C gamma / physiology
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Platelet Activation / drug effects
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Platelet Activation / physiology*
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Platelet Endothelial Cell Adhesion Molecule-1 / genetics
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Platelet Endothelial Cell Adhesion Molecule-1 / physiology*
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Platelet Glycoprotein GPIIb-IIIa Complex / physiology
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Platelet Membrane Glycoproteins / agonists
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Platelet Membrane Glycoproteins / physiology
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Protein Kinase Inhibitors / pharmacology
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Protein-Tyrosine Kinases / blood
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Signal Transduction
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Thrombin / pharmacology
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Viper Venoms / pharmacology
Substances
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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
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Aza Compounds
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CLEC2B protein, human
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Carrier Proteins
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Cross-Linking Reagents
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Lectins, C-Type
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Membrane Glycoproteins
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Morpholines
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Peptides
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Platelet Endothelial Cell Adhesion Molecule-1
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Platelet Glycoprotein GPIIb-IIIa Complex
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Platelet Membrane Glycoproteins
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Protein Kinase Inhibitors
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Viper Venoms
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collagen-related peptide
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platelet membrane glycoprotein VI
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rhodocytin protein, Calloselasma rhodostoma
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Fibrinogen
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Epoprostenol
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Protein-Tyrosine Kinases
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Phospholipase C gamma
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Thrombin