Thrombin-induced increase in surface expression of epitopes on platelet membrane glycoprotein IIb/IIIa complex and GMP-140 is a function of platelet age.
Platelets are heterogeneous in the content of membrane glycoprotein (GP)IIb/IIIa complex. To determine whether this heterogeneity is related to changes associated with platelet aging in the circulation, newly released platelets, obtained during recovery from nonimmune-mediated acute experimental thrombocytopenia in baboons, were studied. Monoclonal antibody (MoAb) binding to epitopes expressed on GPIIb/IIIa complex (LJ-CP8), GMP-140 (S12), and GPIa/IIa (12F1) was measured on control platelets (comprising platelets with a normal age distribution; mean age 60 to 72 hours) and newly formed platelets (mean age 12 hours), both in the resting state and after thrombin stimulation. Whereas LJ-CP8 binding to resting control platelets increased by 34% upon stimulation by gamma-thrombin from 30,885 +/- 1,171 to 41,458 +/- 1,311 molecules/platelet at saturating concentrations of antibody, LJ-CP8 binding to resting young platelets did not increase significantly upon thrombin stimulation (31,878 +/- 3,330 and 33,791 +/- 3,486 molecules/platelet, respectively). Similarly, binding of antibody S12 in response to maximal thrombin stimulation was reduced by 42% from 10,246 +/- 834 molecules/platelet at saturating concentrations of S12 for control platelets to 5,971 +/- 665 molecules/platelet for young platelets (P = .001). S12 binding to unstimulated platelets was less than 10% of the binding observed after thrombin stimulation at all concentrations of S12 for both control and young platelets. However, maximal binding of antibody 12F1 to resting control platelets did not differ significantly from that observed with resting young platelets (2,926 +/- 167 and 2,857 +/- 208 molecules/platelet, respectively), and 12F1 binding was unchanged after thrombin stimulation for both control and young platelets. We conclude that the thrombin-induced increase in the expression of epitopes on platelet membrane GPIIb/IIIa complex and GMP-140 is a function of platelet age.
Savage
B
B
Department of Basic and Clinical Research, Scripps Clinic, La Jolla, CA 92037.
Hunter
C S
CS
Harker
L A
LA
Woods
V L
VL
Hanson
S R
SR
D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000378:metabolism* / Q000502:physiology; D001666:Binding Sites, Antibody; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D002470:Cell Survival; D003594:Cytoplasmic Granules; D000939:Epitopes / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D008297:Male; D019007:P-Selectin; D010215:Papio; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D013917:Thrombin
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D013917:Thrombin