HUMAN KIT-LIGAND (STEM-CELL FACTOR) MODULATES PLATELET ACTIVATION IN-VITRO

The human stem cell factor (SCF), also termed c-Kit ligand (KL), is a hematopoietic growth factor produced by mesenchymal cells that induces proliferation of bone marrow progenitor cells, megakaryocytes, and ma st cells via interaction with c-kit, its cognate receptor Expression o f the c-kit gene was identified in human platelets by the polymerase c hain reaction technique. The presence of the c-Kit receptor was demons trated by the specific binding of I-125-KL/SCF to ADP-stimulated plate lets. The identity of the c-Kit protein was cofirmed by immunoreactivi ty with an anti-c-Kit-specific antibody and by its characterization as a phosphotyrosine containing protein. Under constitutive conditions, was found to be tyrosine-phosphorylated and was associated with a 85-k Da phosphoprotein that could be a fragment of phosphatidylinositol 3-k inase. These data indicate the presence of a new platelet surface mole cule that could function in platelet activation. We demonstrate that t he secondary wave of platelet aggregation and serotonin secretion indu ced by epinephrine and ADP, but not by the thromboxane analog U46619, was augmented by KL/SCF. The effect of KL/SCF on epinephrine/ADP-induc ed platelet activation appeared to be mediated in part through the thr omboxane pathway. These data suggest that KL/SCF could modulate hemost asis via interaction pith platelets, particularly in conditions where mesenchymal cells are exposed to circulating blood elements, such as i n wound healing or atherosclerosis.