DIFFERENTIAL EXPRESSION OF PLATELET ACTIVATION MARKERS IN ASPIRIN-SENSITIVE ASTHMATICS AND NORMAL SUBJECTS

Background Activation of platelets and expression of adhesion molecule s (e.g. CD62P and CD63) which mediate interactions between platelets a nd other cells may be important in the pathogenesis of aspirin-sensiti ve asthma. Objective To determine the expression of CD62P and CD63 on platelets from aspirin-sensitive asthmatic (ASA+), aspirin-tolerant as thmatic (ASA-) and normal subjects and to assess the modulatory effect of aspirin on platelet CD62P and CD63 expression following stimulatio n with either platelet-activating factor (PAF), arachidonic acid (AA) or collagen (COL). Methods Platelet-rich plasma was obtained from 10 A SA+, 10 ASA- and 10 normal control subjects, and expression of CD62P a nd CD63 was measured by flow cytometry. Platelets were stimulated with PAF (10, 80 nM), AA (0.1, 1 mM) or COL (80, 800 mu g/mL) with or with out 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 expre ssion 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 su bjects (P < 0.05) while greater inhibition of CD63 expression was obse rved 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 col lagen-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 a sthma.