THROMBOMODULIN IS SYNTHESIZED BY HUMAN MESANGIAL CELLS

Thrombomodulin (TM), an endothelial receptor for thrombin, endowed wit h a powerful anticoagulant activity, plays an important role in the an tithrombogenicity of the vascular endothelium. Its presence within the human renal glomerulus is already known bur was thought to be only en dothelial. We looked for TM expression in human mesangial cells (MC), both in situ, in freshly prepared glomeruli, and in primary culture. B oth fresh and cultured MC were strongly reactive for TM by immunocytoc hemical methods. Total TM antigen measured on MC lysates and surface T M activity on MC were 0.292 +/- 0.075 ng/mg of cellular proteins and 1 .20 +/- 0.02 pmole of activated protein C/min/mg of cellular proteins, respectively. as shown by the presence of numerous transcripts detect ed by in situ hybridization, TM was shown to be synthesized by MC in v ivo and in culture. The synthesis of active TM by both endothelial and mesangial cells within the renal glomerulus stresses the importance o f its role in maintaining renal hemostatic equilibrium, and sheds some light on the conflicting reports of TM over- and underexpression in g lomerulopathies to open a new field for investigation.