The physiology of platelet secretion has many features in common with the secretory physiology of endocrine and neuronal cells; and a number of the biogenic amines synthesized, stored and secreted by these different cell types are similar. Platelet membrane glycoproteins (GP) appear to be major factors determining cell-cell recognition, and secretion. We have identified a new epitope of GPIb that acts as a receptor for von Willebrand's factor which controls platelet endothelial interaction but does not interfere with platelet secretion or reaction with drug antibodies that also interact with GPIb. In recent years thrombocytopenic states associated with acquired immune deficiency syndrome, post-transfusion purpura, and viral exanthens have been attributed in part to apparent autoantibodies identified by anti-globulin reactions with IgG, IgA, or IgM attached to Western blots of solubilized platelets. We have found a high frequency of identical anti-immunoglobulin bands in normal sera, which appear to be internal (non-plasma membrane) Ig receptors. These receptors in other cells may account for similar apparent autoantibody reactions and in platelets for increases in platelet associated immunoglobulin in diseases of platelet destruction such as ITP. Early events in megakaryopoiesis involving stem cell differentiation, are poorly understood because megakaryocyte progenitors cannot be identified by conventional microscopic techniques. We have found that human leukemic cell lines (HEL and K562), which differentiate into cells that have surface marker glycoproteins similar to platelets also express a growth promoting factor that is similar to the transforming growth factor b-like protein(s) (TGF) from platelets. These conclusions are based on comparisons of platelet TGF and TGF from HEL and K562 by their characteristics on Bio-Gel columns, anchorage-independent growth promoting activity, molecular weights on SDS-PAGE, and amino acid composition. Growth factors appear to play a key role in endothelial repair and homeostasis and are of special importance in diseases of abnormal endothelium such as arteriosclerosis.

Project Start
Project End
Budget Start
Budget End
Support Year
29
Fiscal Year
1986
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code