Biological effects of leukotriene E4 on eosinophils.

John W Steinke, Julie Negri, Spencer C Payne, Larry Borish

Journal: Prostaglandins, leukotrienes, and essential fatty acids 2015;91(3):105-10

PMID: 24768603

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Abstract

Studies demonstrate the existence of novel receptors for cysteinyl leukotrienes (CysLTs) that are responsive to leukotriene (LT) E4 and might be pathogenic in asthma. Given the eosinophilic infiltration in this disorder, we investigated eosinophil expression of P2Y12 and gpr99 and their capacity to respond to LTE4. Receptor transcript expression was investigated via quantitative PCR and surface protein expression via flow cytometry. We investigated LTE4 influences on eosinophils including Ca(+2) flux, cAMP induction, modulation of adhesion molecule expression, apoptosis and degranulation. Eosinophils displayed both transcript and surface protein expression of P2Y12 and gpr99. We could not find evidence of LTE4 activation of eosinophils, however, LTE4 induced cAMP expression, and preincubation of eosinophils with LTE4 inhibited degranulation. Even though eosinophils are an important source of CysLTs in AERD, eosinophils are not themselves the pro-inflammatory biological target and, in contrast, LTE4 via cAMP primarily elicits anti-inflammatory responses.

Address: Carter Immunology Center Asthma and Allergic Disease Center Departments of Medicine, University of Virginia Health Systems, Charlottesville, VA 22908-1355, USA.; Carter Immunology Center Asthma and Allergic Disease Center Departments of Medicine, University of Virginia Health Systems, Charlottesville, VA 22908-1355, USA; Carter Immunology Center Asthma and Allergic Disease Center Departments of Otolaryngology, University of Virginia Health Systems, Charlottesville, VA 22908-1355, USA.; Carter Immunology Center Asthma and Allergic Disease Center Departments of Microbiology, University of Virginia Health Systems, Charlottesville, VA 22908-1355, USA. Electronic address: [email protected].

DOI: 10.1016/j.plefa.2014.02.006

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MeSH Terms: Apoptosis, Cell Adhesion Molecules, Cell Degranulation, Cyclic AMP, Eosinophils, Female, Flow Cytometry, Gene Expression Regulation, Humans, Leukotriene E4, Male, Polymerase Chain Reaction, Receptors, G-Protein-Coupled, Receptors, Purinergic P2, Receptors, Purinergic P2Y12