Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC1

Title: TRPC1 regulates fMLP-stimulated migration and chemotaxis of neutrophil granulocytes.

Authors: O Lindemann, C Strodthoff, M Horstmann, N Nielsen, F Jung, S Schimmelpfennig, M Heitzmann, A Schwab

Journal, date & volume: Biochim. Biophys. Acta, 2015 Sep , 1853, 2122-30

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25595528

Abstract
Neutrophils form the first line of defense of the innate immune system and are rapidly recruited by chemotactic signals to sites of inflammation. Understanding the mechanisms of neutrophil chemotaxis is therefore of great interest for the potential development of new immunoregulatory therapies. It has been shown that members of the transient receptor potential (TRP) family of cation channels are involved in both cell migration and chemotaxis. In this study, we demonstrate that TRPC1 channels play an important role in fMLP mediated chemotaxis and migration of murine neutrophils. The knock-out of TRPC1 channels leads to an impaired migration, transmigration and chemotaxis of the neutrophils. In contrast, Ca²⁺ influx but not store release after activation of the TRPC1(-/-) neutrophils with fMLP is strongly enhanced. We show that the enhanced Ca²⁺ influx in the TRPC1(-/-) neutrophils is associated with a steepened front to rear gradient of the intracellular Ca²⁺ concentration with higher levels at the cell rear. Taken together, this paper highlights a distinct role of TRPC1 in neutrophil migration and chemotaxis. We propose that TRPC1 controls the activity of further Ca²⁺ influx channels and thus regulates the maintenance of intracellular Ca²⁺ gradients which are critical for cell migration. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.