The calcium-conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein-2-induced migration of mouse neutrophils

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Abstract:

Abstract Aim: 

The role of the calcium-conducting ion channel transient receptor potential canonical 6 (TRPC6) in macrophage inflammatory protein-2 (MIP-2) induced migration of mouse neutrophils was investigated. Methods: 

Neutrophil granulocytes isolated from murine bone marrow of wild-type (TRPC6+/+) and TRPC6 knockout (TRPC6−/−) mice were tested for the presence of TRPC6 channel expression using quantitative real-time polymerase chain reactions and immunocytochemistry. The effect of different stimuli (e.g. MIP-2, 1-oleoyl-2-acetyl-sn-glycerol, formyl-methionyl-leucyl-phenylalanin) on migration of isolated neutrophils was tested by two-dimensional (2D) migration assays, phalloidin staining and intracellular calcium imaging. Results: 

We found that neutrophil granulocytes express TRPC6 channels. MIP-2 induced fast cell migration of isolated neutrophils in a 2D cell-tracking system. Strikingly, MIP-2 was less potent in neutrophils derived from TRPC6−/− mice. These cells showed less phalloidin-coupled fluorescence and the pattern of cytosolic calcium transients was altered. Conclusions: 

We describe in this paper for the first time a role for transient receptor potential (TRP) channels in migration of native lymphocytes as a new paradigm for the universal functional role of TRPs. Our data give strong evidence that TRPC6 operates downstream to CXC-type Gq-protein-coupled chemokine receptors upon stimulation with MIP-2 and is crucial for the arrangement of filamentous actin in migrating neutrophils. This is a novel cell function of TRP channel beyond their well-recognized role as universal cell sensors.

Keywords: cell migration; leucocytes; macrophage inflammatory protein-2; neutrophil granulocytes; transient receptor potential canonical 6; transient receptor potential channels

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1748-1716.2008.01918.x

Affiliations: 1:  Department of Molecular Cell Biology, Laboratory of Ion Channel Research, KU Leuven, Leuven, Belgium 2:  Novartis Institutes for BioMedical Research, Novartis Horsham Research Centre, Horsham, West Sussex, UK

Publication date: January 1, 2009

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