Human platelet activation in the absence of aggregation: a calcium-
dependent phenomenon independent of thromboxane formation
S Levy-Toledano, J Maclouf, P Bryon, E Savariau, RM Hardisty and JP Caen
In response to ionophore A 23187, thrombasthenic and EDTA-treated control
platelet-rich plasmas (PRP) undergo a change in light transmission (LT)
accompanied by a normal 14C-serotonin (5HT) release and thromboxane (TX)
synthesis in the absence of aggregation. Ultrastructural qualitative
electron microscopy revealed central apposition of organelles and loosely
packed platelets in both models, while a central gel mass appeared only in
thrombasthenic patients. Quantitative analysis of this ultrastructural
change showed an increase in the elongation and a decrease in the
circularity coefficients of thrombasthenic platelets, indicating a shape
change with pseudopod formation, while EDTA-treated platelets underwent a
shape change in the absence of pseudopod formation. Morphometric analysis
showed that the ionophore caused extensive degranulation in both types of
platelets (decrease of the granule volume), which occurred in the presence
of contraction of thrombasthenic PRP (decrease of the SCS plus granule
volume) but in its absence in EDTA-treated platelets. The change in LT was
not inhibited by aspirin, suggesting a dissociation between release of
14C-5HT and TX formation. Moreover, it was not inhibited by creatine
phosphate plus creatine phosphokinase, prostaglandin E1, or cytochalasin
and/or colchicine. It was not dependent on ADP, cAMP, or the integrity of
microfilaments and microtubules. However, chlorpromazine, TMB 8, and
dibucaine, which interfere with intracellular membrane transport of Ca2+,
inhibited this platelet activation (change in LT, 14C-5HT release and TX
synthesis.
Volume 59,
Issue 5,
pp. 1078-1085,
05/01/1982
Copyright © 1982 by The American Society of Hematology