Phosphoinositide 3-kinase γ mediates chemotactic responses of human eosinophils to platelet-activating factor

Matar Hasan, Anwar; Mourtada-Maarabouni, Mirna; Hameed, Mohammed S.; Williams, Gwyn T.; Dent, Gordon

Abstract

Background
Eosinophils are characteristic participants in allergic inflammation. The intracellular signalling mechanisms involved in the migration of eosinophils to sites of allergic inflammation are poorly understood. Chemotactic responses of eosinophils to platelet-activating factor (PAF), but not eotaxin, have been demonstrated to be dependent upon the activation of phosphoinositide 3-kinase (PI3K) but the specific isoform of PI3K involved has not been identified.

Objective
To determine the roles of the leukocyte-specific PI3Kγ and PI3Kδ isoforms of PI3K in PAF-induced chemotaxis of human eosinophils.

Methods
Chemotactic responses of the EoL-1 eosinophilic cell line and human peripheral blood eosinophils were measured. The effects of a PI3Kγ-selective inhibitor (5-[2,2-difluorobenzo(1,3)dioxol-5-ylmethylene]-thiazolidine-2,4-dione; AS604850) and gene knock-down of PI3Kγ and PI3Kδ on chemotactic responses were determined.

Results
AS604850 caused a concentration-dependent suppression of chemotactic responses of EoL-1 cells and blood eosinophils to PAF but not eotaxin. Specific siRNAs reduced the expression of PI3Kγ and PI3Kδ in EoL-1 cells. Knock-down of PI3Kγ by siRNA resulted in a 75% inhibition of the chemotactic response to PAF but had no effect on the response to eotaxin. Knock-down of endogenous PI3Kδ by siRNA resulted in a 38% inhibition of the chemotactic response to PAF but had no effect on the response to eotaxin.

Conclusion
PI3Kγ plays a major role in the induction of chemotaxis in PAF-stimulated eosinophils, while PI3Kδ plays a lesser role. Interventions which reduce the activity of PI3Kγ may have therapeutic potential in allergic diseases.

Citation

Matar Hasan, A., Mourtada-Maarabouni, M., Hameed, M. S., Williams, G. T., & Dent, G. (2010). Phosphoinositide 3-kinase γ mediates chemotactic responses of human eosinophils to platelet-activating factor. International Immunopharmacology, 10(9), 1017-1021. https://doi.org/10.1016/j.intimp.2010.05.014

• Journal Article Type: Article
• Acceptance Date: May 27, 2010
• Online Publication Date: Jun 4, 2010
• Publication Date: 2010-09
• Deposit Date: May 16, 2024
• Journal: International Immunopharmacology
• Print ISSN: 1567-5769
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 9
• Pages: 1017-1021
• ISBN: 15675769
• DOI: https://doi.org/10.1016/j.intimp.2010.05.014
• Public URL: https://keele-repository.worktribe.com/output/543720
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1567576910001876?via%3Dihub