Abstract
Introduction: Increased antigen-induced bronchoconstriction after cyclooxygenase (COX) inhibition has been observed in animal models and isolated human airways, but the mechanisms involved remain unclear.
Methods: Male albino guinea pigs (GP; n=30) were sensitized to ovalbumin (OVA). Animals were sacrificed 14-28 days later and rings of the trachea (GPT) were isolated and mounted in organ baths for parallel recordings of contractions and measurement of lipid mediator release into the bath fluid by UPLC-MS/MS or EIA.
Results: In GPT, challenge with OVA (100 µg/mL) induced a constrition (Emax of 54±6%) that was enhanced by the unselective COX inhibitor indomethacin (Emax:94±2%; p<0.05). Bath fluid levels of prostaglandins (PG) D2/E2/F2α/I2 and thromboxane (TX) A2 were markedly increased by OVA and abolished by indomethacin (p<0.05). Selective inhibition of COX-2 by lumiracoxib did not inhibit release of PGD2 or TXA2.
The antigen-induced bronchoconstriction was amplified by selective inhibition of PGD synthase, whereas it was reduced by exogenous PGD2 (p<0.05). Moreover, the DP1 receptor agonist BW 245c induced a concentration-dependent reduction of the antigen-induced constriction (Emax:55±12%) accompanied with reduced histamine and CysLT release (p<0.05). The inhibition induced by BW 245c was blocked by the DP1 receptor antagonist MK-524 (Emax:92±4%) concomitant with increased histamine and CysLT levels (p<0.05).
Conclusion: Endogenous PGD2 is generated via COX-1 and mediates a previously unknown inhibitory effect of the antigen-induced bronchoconstriction via DP1 receptors inhibiting mast cell release.
Footnotes
Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 2897.
This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2020