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.

• Authors: Aline Andrea da Cunha, Josiane Silva Silveira, Géssica Luana Antunes, Keila Abreu da Silveira, Rodrigo Benedetti Gassen, Ricardo Vaz Breda, Paulo Márcio Pitrez
• Journal: Experimental lung research (Exp Lung Res) Vol. 47 Issue 8 Pg. 355-367 (10 2021) ISSN: 1521-0499 [Electronic] England
• PMID: 34468256 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Leukotriene Antagonists
• Leukotrienes
• Receptors, Leukotriene
• leukotriene D4 receptor

Topics

• Animals
• Asthma (drug therapy)
• Bronchoalveolar Lavage Fluid
• Disease Models, Animal
• Eosinophils
• Extracellular Traps
• Leukotriene Antagonists (pharmacology)
• Leukotrienes
• Lung
• Mice
• Mice, Inbred BALB C
• Receptors, Leukotriene