Abstracts (complete list) - Wissenschaft Online

Janine Wehrhahn, Robert Kraft, Sunna Hauschildt
Regulation of TRPM2 channels in human monocytes and
macrophages
TRPM2 belongs to the superfamily of transient receptor potential (TRP) proteins and
functions as a calcium-permeable, nonselective cation channel. TRPM2 is specifically
activated by intracellular ADP-ribose and can be opened during oxidant stress.
Here we show for the first time the occurrence of TRPM2 in human monocytes and
monocyte-derived macrophages on mRNA-, protein- and functional level. We studied
freshly isolated monocytes and macrophages in comparison with 16 h cultivated
unstimulated and LPS-stimulated (100ng/ml) cells.
Besides the total TRPM2-mRNA we could detect the splice variants TRPM2-S and TRPM2-
ΔC in both monocytes and macrophages. The splice variant TRPM2-ΔN was absent.
Using semi-quantitative real time PCR we found that in monocytes TRPM2-mRNA was
significantly down-regulated after 16 h cultivation in the absence but not in the
presence of LPS. In human macrophages the TRPM2-mRNA-level was not affected by
different incubation conditions.
Western blot analyses showed that in human monocytes TRPM2 protein expression
follows the same pattern as the mRNA-expression. In macrophages however the TRPM2
protein-level does not exactly mirror the mRNA-level.
Whole-cell patch clamp recordings using ADP-ribose in the pipette solution consistently
revealed TRPM2-like cation currents in both monocytes and macrophages. The
functional activity of TRPM2 correlated with the mRNA and protein data in monocytes
and the mRNA data in macrophages.
The expression and functionality of the cation channel TRPM2 in human monocytes and
macrophages provide a potent mean to regulate intracellular calcium levels and
biological answers. The inhibition of the TRPM2 channel will help to clarify its exact
function in human monocytic cells.