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Aspirin-induced COX-2 overexpression in monocytes of aspirin-intolerant patients
Morgan, Tina ...
Background: We hypothesize that alternate regulation of cyclooxygenase-2 (COX-2) may predispose patients to aspirin-induced exacerbations.Therefore, wewant to examine the dynamics of COX-2 ...up-regulation in whole blood monocytesin the presence and absence of aspirin. Methods: COX-2 expression wasevaluated by flow cytometry through intracellular staining of whole blood monocytes with antiCOX-2 antibodies. Enzyme up-regulation was monitored afterin vitrostimulation with lipopolysaccharide (LPS) and/or aspirin in 19 aspirin-intolerant (AI) patients (8 aspirin-sensitive asthmatics and 11 urticaria-angioedema patients) and 14 healthy controls. Results: We found significantly higher COX-2 expression levels after stimulation with LPS and aspirin (mean 78.8, range 44.9-92.3; p = 0.0002) in comparison to LPS alone (mean 65.9%, range 33.6-82.6) in AI patients. A comparable, but lower up-regulation was also observed after aspirin stimulation alone (median 2.1%, range 0.5-15.9; p = 0.004) in comparison with baseline values (median 1%, range 0.1-5.4). There was no significant difference in COX-2 expression between LPS and aspirin stimulation (mean 61.8%, range 26.8-89.2; p = 0.09) and LPS stimulation (mean 55.5%, range 28.1-74.3) nor between aspirin stimulation alone (median 0.5%, range 0-8.6; p = 0.8) and baseline values (median 0.4%, range 0-5.4) in healthy control subjects. Conclusions: The main finding of this study is that COX-2 appears to be differentially regulated inaspirin-sensitive patients. What is really new is the observation that aspirin and LPS increase COX-2 expression on blood monocytes of AI asthmatics,a finding in contrast with the lack of an effect of the same stimuli on COX-2 expression on monocytes from healthy subjects.
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