title: Differential expression of platelet activation markers in aspirin-sensitive asthmatics and normal subjects.
abstract: 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.
authors.affiliation: Department of Medicine, University of Western Australia, Nedlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Taylor
authors.forename: N L
authors.initials: NL
authors.lastname: Misso
authors.forename: G A
authors.initials: GA
authors.lastname: Stewart
authors.forename: P J
authors.initials: PJ
authors.lastname: Thompson
mesh_terms: 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
chemical_list: 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