Channelpedia

PubMed 23636057


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC6



Title: TRPC6 regulates CXCR2-mediated chemotaxis of murine neutrophils.

Authors: Otto Lindemann, Daniel Umlauf, Svetlana Frank, Sandra Schimmelpfennig, Jessica Bertrand, Thomas Pap, Peter J Hanley, Anke Fabian, Alexander Dietrich, Albrecht Schwab

Journal, date & volume: J. Immunol., 2013 Jun 1 , 190, 5496-505

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23636057


Abstract
Unraveling the mechanisms involved in chemotactic navigation of immune cells is of particular interest for the development of new immunoregulatory therapies. It is generally agreed upon that members of the classical transient receptor potential channel family (TRPC) are involved in chemotaxis. However, the regulatory role of TRPC channels in chemoattractant receptor-mediated signaling has not yet been clarified in detail. In this study, we demonstrate that the TRPC6 channels play a pronounced role in CXCR2-mediated intermediary chemotaxis, whereas N-formyl-methionine-leucine-phenylalanine receptor-mediated end-target chemotaxis is TRPC6 independent. The knockout of TRPC6 channels in murine neutrophils led to a strongly impaired intermediary chemotaxis after CXCR2 activation which is not further reinforced by CXCR2, PI3K, or p38 MAPK inhibition. Furthermore, CXCR2-mediated Ca(2+) influx but not Ca(2+) store release was attenuated in TRPC6(-/-) neutrophils. We demonstrate that the TRPC6 deficiency affected phosphorylation of AKT and MAPK downstream of CXCR2 receptor activation and led to altered remodeling of actin. The relevance of this TRPC6-depending defect in neutrophil chemotaxis is underscored by our in vivo findings. A nonseptic peritoneal inflammation revealed an attenuated recruitment of neutrophils in the peritoneal cavity of TRPC6(-/-) mice. In summary, this paper defines a specific role of TRPC6 channels in CXCR2-induced intermediary chemotaxis. In particular, TRPC6-mediated supply of calcium appears to be critical for activation of downstream signaling components.