Uncoupled regulation of leukotriene C₄ synthase in platelets from aspirin‐intolerant asthmatics and healthy volunteers after aspirin treatment

Abstract

The results indicate that oral aspirin administration can lead to uncoupling of thromboxane A2-dependent negative feedback mechanisms, which may normally restrict the production of cysteinyl leukotrienes. This mechanism can be of potential interest in aspirin-induced asthma.

TBXA2R gene polymorphism and responsiveness to leukotriene receptor antagonist in children with asthma

“…Recent studies have shown that ongoing TBXA2 production can suppress LTC 4 synthase activity in eosinophils and smooth muscle cells, as well as in platelets, and is paralleled by suppressed levels of leukotriene [14,21]. These findings suggest that TBXA2 and TBXA2R polymorphisms may be related to leukotriene-dependent phenotypes of asthma such as AIA and asthma with EIB.…”

“…In contrast to leukotriene, the role of TBXA2 in EIB has been poorly understood, but a recent study has demonstrated that attenuation of TBXA2 biosynthesis can lead to increased formation of leukotriene via uncoupling of LTC 4 synthase down-regulation in patients with AIA [14]. Thus, it is postulated that TBXA2 is a negative regulator of LTC 4 synthase, which leads to LT synthesis.…”

“…Recent studies have shown that TBXA2 can be considered a negative regulator of LTC 4 synthase activity, which is responsible for leukotriene production, and have also suggested that when TBXA2 formation is prevented, LTC 4 synthase activity is elevated, leading to increased biosynthesis of leukotriene and clinical symptoms [11][12][13][14].…”

Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease

“…In the aspirin challenge test aspirin further suppresses prostaglandin E 2 synthesis and uncouples the downregulation of LTC 4 S activity through inhibition of TXA 2 formation. 45 Additionally, arachidonic acid derived from adherent platelets activates 5-lipoxygenase in granulocytes and results in cysLT overproduction in patients with AERD (see Fig E3). 35 The results of our study suggest that antiplatelet therapy, especially with P-selectin antagonist, could be therapeutically beneficial in patients with AERD.…”

Hypersensitivity to Aspirin and Other Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

“…It has been reported that platelets from NSAID hypersensitive patients present a modified H2O2 metabolism [87] as well as some other indications of platelet involvement [88,89] but whether such alterations play a role in the generation of clinical symptoms is not ascertained.…”