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Differential expression of platelet activation markers in aspirin-sensitive asthmatics and normal subjects
M L Taylor1, N L Misso, G A Stewart
1Department of Medicine, University of Western Australia, Nedlands.
Insights
Platelets in aspirin-sensitive asthma show increased CD62P expression, which aspirin can inhibit more effectively. This suggests a role for platelet activation in aspirin-sensitive asthma pathogenesis.
Area of Science:
- Immunology
- Hematology
- Pulmonology
Background:
- Platelet activation and adhesion molecule expression (CD62P, CD63) are implicated in aspirin-sensitive asthma pathogenesis.
- Understanding these mechanisms can reveal therapeutic targets.
Purpose of the Study:
- To quantify CD62P and CD63 expression on platelets in aspirin-sensitive asthmatic (ASA+), aspirin-tolerant asthmatic (ASA-), and normal subjects.
- To evaluate aspirin's effect on platelet CD62P and CD63 expression after stimulation with platelet-activating factor (PAF), arachidonic acid (AA), or collagen (COL).
Main Methods:
- Flow cytometry was used to measure CD62P and CD63 expression on platelets from 10 ASA+, 10 ASA-, and 10 control subjects.
- Platelets were stimulated with PAF, AA, or COL, with or without varying concentrations of aspirin.
Main Results:
- ASA+ patients exhibited higher AA- and collagen-induced CD62P expression than controls.
- ASA- patients showed reduced CD62P and CD63 expression compared to ASA+ and controls.
- Aspirin more effectively inhibited CD62P expression in ASA+ patients compared to ASA- and control subjects.
Conclusions:
- Elevated AA- and collagen-induced platelet CD62P in ASA+ patients and enhanced aspirin inhibition of CD62P are potentially key to aspirin-sensitive asthma.
- Reduced platelet CD62P/CD63 in ASA- patients may indicate different pathogenic pathways in other asthma types.
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.