Premium
The calcium‐conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein‐2‐induced migration of mouse neutrophils *
Author(s) -
Damann N.,
Owsianik G.,
Li S.,
Poll C.,
Nilius B.
Publication year - 2009
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2008.01918.x
Subject(s) - trpc6 , transient receptor potential channel , microbiology and biotechnology , chemistry , receptor , calcium in biology , calcium , chemotaxis , chemokine , biophysics , biology , biochemistry , organic chemistry
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 G q ‐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.