An anti-inflammatory drug, propagermanium, may target GPI-anchored proteins associated with an MCP-1 receptor, CCR2

Monocyte chemoattractant protein-1 (MCP-1) promotes the migration and activ ation of monocytes and plays a pivotal role in the development of chronic i nflammation. Propagermanium (3-oxygermylpropionic acid polymer) has been us ed as a therapeutic agent against chronic hepatitis B in Japan. We report h ere that propagermanium specifically inhibits in vitro chemotactic migratio n of monocytes by MCP-1, Propagermanium did not inhibit binding of MCP-1 to a human monocytic cell line, THP-1 cells, or affect intracellular Ca2+ mob ilization or the cAMP concentration in MCP-1-treated THP-1 cells. The effec t of propagermanium seems to require glycosylphosphatidylinositol (GPI)-anc hored proteins, as cleavage of GPI anchors by phosphatidyl-inositol-phospho lipase C (PI-PLC) eliminated the inhibitory activity of propagermanium, Ant i-GPI-anchored protein antibodies, such as anti-CD55 and anti-CD59, reduced staining of C-C chemokine receptor 2 (CCR2) with an anti-CCR2 antibody aga inst the N-terminus of CCR2 in a flow cytometric analysis, and these antibo dies also selectively inhibited MCP-1-induced migration of THP-1 cells. Fur thermore, under fluorescence microscopy, GPI-anchored proteins colocalized with CCR2 on THP-1 cells. These results suggest that propagermanium may tar get GPI-anchored proteins that are closely associated with CCR2 to selectiv ely inhibit the MCP-1-induced chemotaxis, thus providing a mechanistic basi s for the anti-inflammatory effects of the drug.