A FUNCTIONAL TETHERED LIGAND THROMBIN RECEPTOR IS PRESENT ON HUMAN HEMATOPOIETIC PROGENITOR CELLS

The professing of inflammatory signals occurs through a variety of mec hanisms; the recent descriptions of the tethered ligand receptor fur t hrombin (JA Hoxie et al., J Biol Chem 268:13756, and TK Vu et al., Cel l 64:1057) provide a novel route and mechanism for cellular activation after inflammation and thrombosis. Using standard flow-cytomeric tech niques, it has been shown that the tethered ligand receptor is found o n a number of terminally differentiated hematopoietic cells including platelets, lymphocytes, and monocytes. In this paper, we show that the CD34(+) subset of hematopoietic stem cells bears the tethered ligand receptor on its surface; in addition, stimulation of this receptor wit h the agonist peptide SFLLRN results in a dose-dependent increase in i ntracellular calcium levels. We also show that culturing bone marrow m ononuclear cells in the presence of thrombin or the tethered Ligand re ceptor agonist peptide results in a statistically significant increase in colony-forming units-erythroid and -granulocyte/macrophage (CFU-E and CFU-GM). Although more work is needed to establish the exact mecha nism of this effect, our results suggest that activation of the tether ed ligand thrombin receptor may modulate the proliferative responses o f CD34(+) hematopoietic progenitor cells.