Involvement of the a/ß Isoform of p38 MAP Kinase in Chemotactic Responses of Human Eosinophils to Eotaxin (CCL11) and RANTES (CCL5)

Hasan, Anwar M; Dent, Gordon

Abstract

Eosinophils are the principal effector cells for allergic inflammation in a variety of diseases, in which they contribute to tissue damage and remodelling processes via the secretion of cytotoxic granular proteins and cytokines. The intracellular mechanisms that control the activation, recruitment and survival of eosinophils are fundamental in understanding these disease processes. Phosphoinositide 3-kinase (PI3K) has been shown previously to be essential for eosinophil chemotactic responses to some stimuli but not others. Human blood neutrophils have been shown to utilize two antagonistic signalling pathways for chemotaxis: PI3K and p38 mitogen-activated protein kinase (p38 MAPK). In the present study, the role of p38 MAPK in chemotactic responses of an eosinophildifferentiated myeloid leukaemia cell line (EOL-1) and human peripheral blood eosinophils to a range of stimuli - platelet-activating factor (PAF), eotaxin 1 (CCL11), RANTES (CCL5), interleukin 8 (IL8, CXCL8) and IL16 - was explored through the use of the p38 MAPK a/ß isoform inhibitor, SB 203580. SB 203580 caused significant inhibition of chemotactic responses of both EOL-1 cells and blood eosinophils to eotaxin 1 and RANTES (=75% inhibition at 1 µM SB 203580, p<0.01) but had no effect on the migration induced by PAF and IL16 (<25%) and little or no effect on responses to IL8. Responses to PAF - but not
eotaxin - have been shown previously to be suppressed by PI3K inhibition. The complementary pattern of inhibition observed in the present study provides evidence that distinct PI3K-dependent and p38 MAPK-dependent chemoattractants may also exist for eosinophils.

Citation

Hasan, A. M., & Dent, G. (2017). Involvement of the a/ß Isoform of p38 MAP Kinase in Chemotactic Responses of Human Eosinophils to Eotaxin (CCL11) and RANTES (CCL5). American Journal of Immunology, 209-215. https://doi.org/10.3844/ajisp.2017.209.215

• Journal Article Type: Article
• Acceptance Date: Oct 19, 2017
• Online Publication Date: Oct 26, 2017
• Publication Date: Oct 26, 2017
• Journal: American Journal of Immunology
• Electronic ISSN: 1558-3775
• Publisher: Science Publications
• Peer Reviewed: Peer Reviewed
• Pages: 209-215
• DOI: https://doi.org/10.3844/ajisp.2017.209.215
• Keywords: Eosinophils, Chemotaxis, Cell Signalling, p38 MAP Kinase
• Publisher URL: https://doi.org/10.3844/ajisp.2017.209.215