Differential expression of platelet activation markers in aspirin-sensitive asthmatics and normal subjects.
BACKGROUND
Activation of platelets and expression of adhesion molecules (e.g. CD62P and CD63) which mediate interactions between platelets and other cells may be important in the pathogenesis of aspirin-sensitive asthma.


OBJECTIVE
To determine the expression of CD62P and CD63 on platelets from aspirin-sensitive asthmatic (ASA+), aspirin-tolerant asthmatic (ASA-) and normal subjects and to assess the modulatory effect of aspirin on platelet CD62P and CD63 expression following stimulation with either platelet-activating factor (PAF), arachidonic acid (AA) or collagen (COL).


METHODS
Platelet-rich plasma was obtained from 10 ASA+, 10 ASA- and 10 normal control subjects, and expression of CD62P and CD63 was measured by flow cytometry. Platelets were stimulated with PAF (10, 80 nM), AA (0.1, 1 mM) or COL (80, 800 micrograms/mL) with or without aspirin (concentration range 0.4-4 mg/mL).


RESULTS
In the absence of aspirin, CD62P expression induced by AA and COL was greater in ASA+ patients compared with control subjects (P < 0.001) while CD62P expression with PAF, AA and COL was reduced in ASA- when compared with ASA+ and control subjects (P < 0.001). CD63 expression with PAF and AA was reduced in both ASA+ and ASA- patients compared with control subjects (P < 0.001). Aspirin inhibited the expression of both CD62P and CD63 after agonist stimulation. Greater inhibition of CD62P expression was observed in ASA+ compared with ASA- patients (P < 0.001) and normal subjects (P < 0.05) while greater inhibition of CD63 expression was observed in normal subjects compared with both ASA+ and ASA- patients (P < 0.05). In ASA+ patients and normal subjects, stimulation with PAF and COL resulted in only one platelet population while in contrast with 1 mM AA two populations were observed.


CONCLUSIONS
Enhanced AA- and collagen-induced platelet CD62P expression in ASA+ patients compared with normal subjects and greater inhibition by aspirin of CD62P expression in ASA+ may be relevant to the pathogenesis of this syndrome. Reduced expression of CD62P and CD63 in platelets of ASA- patients following stimulation with PAF and AA may also have implications for the role of platelets and these mediators in the pathogenesis of other forms of asthma.
Taylor
M L
ML
Department of Medicine, University of Western Australia, Nedlands.
Misso
N L
NL
Stewart
G A
GA
Thompson
P J
PJ
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000209:etiology / Q000503:physiopathology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D004342:Drug Hypersensitivity / Q000209:etiology / Q000503:physiopathology*; D004347:Drug Interactions; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D060149:Tetraspanin 30
D015703:Antigens, CD; C554586:CD63 protein, human; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D016718:Arachidonic Acid; D003094:Collagen; D001241:Aspirin