This paper is dedicated to Professor Ole H. Petersen to admirable his pioneering and admiring work on Ca2+ signalling and the whole cellular physiology and pathophysiology.
The calcium-conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein-2-induced migration of mouse neutrophils*
Version of Record online: 28 OCT 2008
© 2008 The Authors. Journal compilation © 2008 Scandinavian Physiological Society
Special Issue: International Symposium on Frontiers in Physiology
Volume 195, Issue 1, pages 3–11, January 2009
How to Cite
Damann, N., Owsianik, G., Li, S., Poll, C. 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, 195: 3–11. doi: 10.1111/j.1748-1716.2008.01918.x
- Issue online: 9 DEC 2008
- Version of Record online: 28 OCT 2008
- Received 19 May 2008, accepted 21 June 2008
- cell migration;
- macrophage inflammatory protein-2;
- neutrophil granulocytes;
- transient receptor potential channels;
- transient receptor potential canonical 6
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.