ADP causes partial degranulation of platelets in the absence of aggregation.
Whole blood flow cytometry has revealed that platelets undergo partial degranulation in response to ADP, in the absence of aggregation, as evidenced by the expression of the P-selectin and CD63 antigens of the alpha-granule and lysosomal membranes respectively. With maximum ADP (10(-5) M) fibrinogen bound to 76.1 +/- 7.2% of platelets but P-selectin and CD63 antigen were expressed on 26.9 +/- 9.8% and 8.6 +/- 3.5% of platelets respectively. Maximum fibrinogen binding, P-selectin and CD63 expression induced by alpha-thrombin were 96.1 +/- 1.4%, 92.8 +/- 2.3% and 77.6 +/- 9.7% respectively. beta-thromboglobulin release from the ADP-stimulated platelets correlated closely with the expression of P-selectin and CD63 (r = 0.98 +/- 0.02 for both antigens). No platelet aggregates were seen by flow cytometry and the absence of aggregation was confirmed by single cell counting. Addition of the GPIIb-IIIa antagonist echistatin, at concentrations that totally blocked fibrinogen binding to ADP-stimulated platelets, had no effect on the expression of the granule membrane antigens. The partial degranulation of normal platelets was independent of thrombin generation since it was not inhibited by hirudin (5 units/ml). In conclusion, ADP is capable of causing partial degranulation of platelets independently of aggregation, fibrinogen binding or thrombin generation. Thus release of potent procoagulant, vasoactive and mitogenic substances from the platelets could continue in the presence of thrombin inhibitors and GPIIb-IIIa antagonists.
Janes
S L
SL
Academic Department of Haematology, Royal Free Hospital and School of Medicine, London.
Wilson
D J
DJ
Cox
A D
AD
Chronos
N A
NA
Goodall
A H
AH
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D015703:Antigens, CD / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D015550:Cell Degranulation / Q000187:drug effects*; D005340:Fibrinogen / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D019007:P-Selectin; D010974:Platelet Aggregation / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000097:blood; D060149:Tetraspanin 30; D013917:Thrombin / Q000502:physiology; D001620:beta-Thromboglobulin / Q000378:metabolism
D015703:Antigens, CD; C554586:CD63 protein, human; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D001620:beta-Thromboglobulin; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D013917:Thrombin