Close relationship between the platelet activation marker CD62 and the granular release of platelet-derived growth factor.
The expression of CD62 on the surface of platelets is considered to be an indicator of platelet degranulation and secretion. We characterized the relationship between CD62 expression and platelet-derived growth factor (PDGF)(AB) and PDGF(BB) secretion in response to thrombin-receptor activating peptide (TRAP). The principal findings were 1) expression of CD62 as a constituent of platelet alpha-granule membrane and secretion of PDGF, an important ingredient of alpha-granules, can be stimulated by TRAP-induced activation in a dose-dependent fashion; 2) the activation marker and secretion product are closely correlated with each other; and 3) changes in the CD62 expression induced by a drug, namely clopidogrel, or by a disease, namely diabetes, are paralleled by changes in PDGF secretion. Although CD62 is perceived as an activation marker of platelets indicating enhanced aggregability and secretion of alpha-granular content, the proof that the CD62 status and its modifications reflect directly the actual secretion of the most important platelet mitogen, PDGF, has so far not been given. This ex vivo-in vitro study shows that at least for the activation pathway provided by the PAR-1 receptor for which TRAP is the selective agonist, CD62 expression on platelets could be a surrogate for their secretory activity.
Graff
Jochen
J
Institute of Clinical Pharmacology, University Hospital, Frankfurt/Main, Germany.
Klinkhardt
Ute
U
Schini-Kerth
Valérie B
VB
Harder
Sebastian
S
Franz
Nicole
N
Bassus
Steffen
S
Kirchmaier
Carl M
CM
D000077284:Abciximab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D000077144:Clopidogrel; D003594:Cytoplasmic Granules / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019007:P-Selectin / Q000096:biosynthesis* / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010982:Platelet-Derived Growth Factor; C086309:thrombin receptor peptide SFLLRNP; D000077144:Clopidogrel; D013988:Ticlopidine; D000077284:Abciximab