A functional tethered ligand thrombin receptor is present on human hematopoietic progenitor cells.
The processing of inflammatory signals occurs through a variety of mechanisms; the recent descriptions of the tethered ligand receptor for thrombin (JA Hoxie et al., J Biol Chem 268:13756, and TK Vu et al., Cell 64:1057) provide a novel route and mechanism for cellular activation after inflammation and thrombosis. Using standard flow-cytometric techniques, it has been shown that the tethered ligand receptor is found on 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 with the agonist peptide SFLLRN results in a dose-dependent increase in intracellular calcium levels. We also show that culturing bone marrow mononuclear cells in the presence of thrombin or the tethered ligand receptor 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 mechanism of this effect, our results suggest that activation of the tethered ligand thrombin receptor may modulate the proliferative responses of CD34+ hematopoietic progenitor cells.
DiCuccio
M N
MN
Duke University School of Medicine, Durham, NC, USA.
Shami
P
P
Hoffman
M
M
D015703:Antigens, CD; D018952:Antigens, CD34; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007937:Leukapheresis; D008024:Ligands; D010446:Peptide Fragments / Q000494:pharmacology; D018179:Receptors, Thrombin / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology; D014182:Transplantation, Autologous
D015703:Antigens, CD; D018952:Antigens, CD34; D008024:Ligands; D010446:Peptide Fragments; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); D013917:Thrombin; D002118:Calcium