Cysteinyl‐leukotrienes contribute to sputum eosinophil chemotactic activity in asthmatics

Abstract

Background: Cysteinyl-leukotrienes are lipid derived mediators involved in asthma. They are able to stimulate eosinophil chemotaxis in vitro. Induced sputum from asthmatics has been shown to contain eosinophil chemotactic activity. The purpose of our study was to evaluate the contribution of cysteinyl-leukotrienes to sputum eosinophil chemotactic activity in asthmatics and to seek whether there might be differences between asthmatics free of inhaled corticosteroids vs those regularly receiving this treatment. Methods: Twenty-two patients (11 corticosteroid free, mean FEV 1 99% predicted, 11 corticosteroid-treated, mean FEV 1 77% predicted) recruited from our asthma clinic underwent a sputum induction. Sputum was processed according to standard procedure. Eosinophil chemotactic activity contained in the fluid phase was assessed using Boyden microchamber model and expressed as chemotaxis index (CI). Cysteinyl-leukotrienes were measured in sputum supernatant by ELISA and their role in sputum eosionophil chemotactic activity was evaluated by using montelukast, a selective antagonist of a cys-LT1 receptor. Results: Cysteinyl-leukotrienes were well detectable in sputum supernatants from both steroid-naive (247 ± 42 pg/ml) and steroid-treated (228 ± 26 pg/ml) asthmatics. Sputum eosinophil chemotactic activity was indiscriminately present in both corticosteroid-naive (CI: 2.61 ± 0.22) and corticosteroid-treated (2.98 ± 0.35) asthmatics. Montelukast (100 µM) significantly inhibited the eosinophil chemotactic activity in both groups achieving a mean inhibition of 54.2 ± 9.2% (P < 0.001) and 64.7 ± 7.8% (P < 0.001) in steroid-naive and steroid-treated asthmatics respectively. Conclusion: Cysteinyl-leukotrienes actively participate in sputum eosinophil chemotactic activity found in asthmatics irrespective of whether they are or not under treatment with inhaled corticoids.

Eosinophil Chemokines and Clara Cell Protein 16 Production in Nasal Mucosa of Patients with Persistent Allergic Rhinitis

“…Previous investigations have established that eotaxins induce maximal transendothelial eosinophil migration, with respect to the other chemokines in the following order of strength: eotaxin-2>RANTES>MCP-4>IL-5>LTB4 [16][17][18][19]. Many chemokines act by binding to the several receptors, whereas all eotaxins operate by stimulation of the same receptor, CCR3 [20].…”

Eosinophil Superoxide Anion Generation Induced by Adhesion Molecules and Leukotriene D₄

“…In the tissues at sites of allergic inflammation, a variety of inflammatory cells, including eosinophils, likely generate cysLTs, therefore the eosinophils in such tissues may be exposed to higher concentrations of cysLTs than those measured in the sputum samples. In this context, Hemelaers et al [24] recently reported that eosinophil chemotactic activity in the sputum from both corticosteroid-naive and corticosteroid-treated asthmatic patients was inhibited by montelukast, suggesting that cysLT actively participated in the eosinophil chemotactic activity in the asthmatic airway.…”

Levels of prostaglandin E2 and Cysteinyl‐leukotrienes in sputum supernatant of patients with asthma: the effect of smoking

“…No association was observed between Cyst-LTs and eosinophils in non-smoking asthmatics. This might be due to the lower levels of CystLTs, as there is evidence that Cyst-LTs contribute actively in sputum eosinophilic activity in asthma [26].…”