Thrombin-induced increase in surface expression of epitopes on platelet
membrane glycoprotein IIb/IIIa complex and GMP-140 is a function of
platelet age
B Savage, CS Hunter, LA Harker, VL Woods and SR Hanson
Department of Basic and Clinical Research, Scripps Clinic, La Jolla, CA
92037.
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.
Volume 74,
Issue 3,
pp. 1007-1014,
08/15/1989
Copyright © 1989 by The American Society of Hematology
