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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Damann, N, Owsianik, G, Li, S, Poll, Chris and Nilius, B (2009) The calcium-conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein-2-induced migration of mouse neutrophils. Acta physiologica (Oxford, England), 195 (1). pp. 3-11. ISSN 1748-1716
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 celltracking 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.
| Item Type: | Article |
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| Keywords: | cell migration ; leucocytes ; macrophage inflammatory protein-2 ; neutrophil granulocytes ; transient receptor potential channels ; transient receptor potential canonical 6 |
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| Date Deposited: | 14 Dec 2009 13:48 |
| Last Modified: | 14 Dec 2009 13:48 |
| URI: | https://oak.novartis.com/id/eprint/1454 |