Taylor M L, Misso N L, Stewart G A, Thompson P J
Department of Medicine, University of Western Australia, Nedlands.
Clin Exp Allergy. 1996 Feb;26(2):202-15. doi: 10.1111/j.1365-2222.1996.tb00081.x.
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.
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).
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).
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.
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.
血小板的激活以及介导血小板与其他细胞间相互作用的黏附分子（如CD62P和CD63）的表达，在阿司匹林敏感性哮喘的发病机制中可能起重要作用。
测定阿司匹林敏感性哮喘患者（ASA+）、阿司匹林耐受性哮喘患者（ASA-）和正常受试者血小板上CD62P和CD63的表达，并评估阿司匹林对血小板激活因子（PAF）、花生四烯酸（AA）或胶原（COL）刺激后血小板CD62P和CD63表达的调节作用。
从10例ASA+患者、10例ASA-患者和10名正常对照受试者获取富血小板血浆，采用流式细胞术检测CD62P和CD63的表达。血小板分别用PAF（10、80 nM）、AA（0.1、1 mM）或COL（80、800 μg/mL）刺激，同时或不同时加入阿司匹林（浓度范围0.4 - 4 mg/mL）。
在无阿司匹林的情况下，与对照受试者相比，AA和COL诱导的ASA+患者CD62P表达更高（P < 0.001），而与ASA+患者和对照受试者相比，PAF、AA和COL刺激下ASA-患者的CD62P表达降低（P < 0.001）。与对照受试者相比，PAF和AA刺激下ASA+和ASA-患者的CD63表达均降低（P < 0.001）。激动剂刺激后，阿司匹林抑制CD62P和CD63的表达。与ASA-患者（P < 0.001）和正常受试者（P < 0.05）相比，ASA+患者对CD62P表达的抑制作用更强；与ASA+和ASA-患者相比，正常受试者对CD63表达的抑制作用更强（P < 0.05）。在ASA+患者和正常受试者中，PAF和COL刺激仅产生一个血小板群体，而与1 mM AA刺激相反，观察到两个群体。
与正常受试者相比，ASA+患者中AA和胶原诱导的血小板CD62P表达增强，且ASA+患者中阿司匹林对CD62P表达的抑制作用更强，这可能与该综合征的发病机制有关。PAF和AA刺激后，ASA-患者血小板中CD62P和CD63表达降低，这也可能对血小板及这些介质在其他形式哮喘发病机制中的作用有影响。
