Abstracts (complete list) - Wissenschaft Online

Kristina Wiege, Syed Raza Ali, Stephanie Konrad, Roland Piekorz, Bernd Nürnberg,
Reinhold E Schmidt, J Engelbert Gessner
MECHANISM OF CELL AND ISOTYPE SPECIFIC Gαi DEPENDENT
SIGNALING IN IMMUNE EFFECTOR CELLS
G-protein- coupled receptor (GPCR) signal transduction contributes to the course of
inflammation processes. In the context of immune complex (IC) mediated lung
inflammation the GPCR, the complement 5a receptor (C5aR) is significantly involved in
lung pathology. Previous experimental data verified pertussis toxin sensitive FcRγ
regulation by C5aR suggesting for Gαi -dependent signal transduction mechanism. From
the three known isoforms of inhibitory Gαi proteins, Gαi2 and Gαi3 but not Gαi1 are
expressed on alveolar leukocytes, including macrophages (AM) and neutrophils with the
exception of a splice variant of Gαi2 (sGαi2 ) which appearance is restricted to AM. Mainly
Gαi2 appears to be involved in the regulation IC mediated inflammation. Genetic
deletion of Gαi2 resulted in reduced lung inflammation whereas it was unaffected in
mice lacking Gαi3 . On AM from Gαi2 deficient mice C5aR expression was reduced; this
was not seen for neutrophils, suggesting cell and isotype specific functions of (s)Gαi2 /
Gαi3 . To verify the role of the different isotypes we are using the RNA-Interference
technique. We could demonstrate that the knock down of Gαi2 mRNA leads to the
reduced expression of C5aR on peritoneal macrophage cell line. This effect could be
rescued by the overexpression of Gαi2 . Future work comprises the analysis of sGαi2 and
Gαi3 overexpression in Gαi2 knock down cells to clarify the role of the specific isoforms
on the trafficking and functioning of the C5aR.
Part of the work was supported to K.W. by graduate program (GRK705) of the Deutsche
Forschungsgemeinschaft