Cysteinyl leukotriene induces eosinophil extracellular trap formation via cysteinyl leukotriene 1 receptor in a murine model of asthma

Abstract

Purpose

Eosinophils are one of the main cells responsible to the inflammatory response in asthma by the release of inflammatory molecules such as cytokines, reactive oxygen species (ROS), cytotoxic granule, eosinophil extracellular trap (EET), and lipid mediators as cysteinyl leukotriene (cysLT). The interconnections between these molecules are not fully understood. Here, we attempted to investigate the cysLT participation in the mechanisms of EET formation in an asthma model of OVA challenge.

Materials and methods

Before intranasal challenge with OVA, BALB/cJ mice were treated with a 5-lipoxygenase-activating protein (FLAP) inhibitor (MK-886), or with a cysLT1 receptor antagonist (MK-571) and the lung and bronchoalveolar lavage fluid (BALF) were analyzed.

Results

We showed that OVA-challenged mice treated with MK-886 or MK-571 had a decrease in inflammatory cells, goblet cells hyperplasia, and eosinophil peroxidase (EPO) activity in the airway. However, only OVA-challenged mice treated with MK-571 had an improvement in lung function. Also, treatments with MK-886 or MK-571 decreased Th2 cytokines levels in the airway. Moreover, we observed that OVA-challenged mice treated with MK-886 or MK-571 had a decrease in EET formation in BALF. We also verified that EET release was not due to cell death because the cell viability remained the same among the groups.

Conclusion

We revealed that the decrease in cysLT production or cysLT1 receptor inhibition by MK-886 or/and MK-571 treatments, respectively reduced EET formation in BALF, showing that cysLT regulates the activation process of EET release in asthma.

Keywords:

• Asthma
• cysteinyl leukotriene
• eosinophil extracellular trap
• MK-886
• MK-571

Disclosure statement

The authors declare that they have no commercial or financial conflict of interests.

Additional information

Funding

This study was funded in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) (No. AUXPE‐PNPD 2787/2010) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (No. 132347/2017‐2).