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

• Published in: International immunopharmacology Vol. 10; no. 9; pp. 1017 - 1021
• Main Authors: Hasan, Anwar Matar, Mourtada-Maarabouni, Mirna, Hameed, Mohammed S, Williams, Gwyn T, Dent, Gordon
• Format: Journal Article
• Language: English
• Published: 01-09-2010
• Subjects: 1-Phosphatidylinositol 3-kinase
• ISSN: 1567-5769
• DOI: 10.1016/j.intimp.2010.05.014

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 PI3Kg and PI3Kd 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 PI3Kg-selective inhibitor (5-[2,2-difluorobenzo(1,3)dioxol-5-ylmethylene]-thiazolidine-2,4-d i one; AS604850) and gene knock-down of PI3Kg and PI3Kd 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 PI3Kg and PI3Kd in EoL-1 cells. Knock-down of PI3Kg 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 PI3Kd by siRNA resulted in a 38% inhibition of the chemotactic response to PAF but had no effect on the response to eotaxin. Conclusion - PI3Kg plays a major role in the induction of chemotaxis in PAF-stimulated eosinophils, while PI3Kd plays a lesser role. Interventions which reduce the activity of PI3Kg may have therapeutic potential in allergic diseases.