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Thromboxane A2 causes feedback amplification involving extensive
thromboxane A2 formation on close contact of human platelets in media with
a low concentration of ionized calcium
MA Packham, RL Kinlough-Rathbone and JF Mustard
Close platelet-to-platelet contact induced by weak agonists in a medium
with a low concentration of Ca2+ leads to thromboxane A2 (TXA2) formation,
release of granule contents, and secondary aggregation. These responses do
not occur in a medium containing Ca2+ in the physiological range (1 to 2
mmol/L). Experiments were done to determine whether feedback amplification
is required to generate amounts of TXA2 that are sufficient to cause
secondary aggregation and the reactions associated with it, or whether
close platelet-to-platelet contact alone is sufficient to generate enough
TXA2 to produce these responses. Platelets were washed and resuspended in a
modified Tyrode solution to which no calcium salt was added that contained
0.35% albumin and apyrase. This medium contains 20 mumol/L Ca2+ and 1
mmol/L Mg2+. Platelets were aggregated with adenosine diphosphate (ADP) in
the presence of fibrinogen, agglutinated with polylysine, or after
pretreatment with chymotrypsin, aggregated with fibrinogen. In the low-
Ca2+ medium, all these agonists caused platelets to adhere to each other,
followed by secondary aggregation with TXA2 formation and release of
granule contents. When Ca2+ (1 to 2 mmol/L), aspirin, or the thromboxane
receptor blocker BM 13.177 was present, the secondary responses did not
occur; dazoxiben decreased thromboxane formation, but did not prevent
secondary aggregation or release. Aspirin-treated platelets were less
responsive to ADP, U46619, or TXA2 in the low-Ca2+ medium, which indicated
that the secondary responses of untreated platelets were not caused by a
generalized increase in sensitivity. The reactions that result from close
platelet-to-platelet contact in a low- Ca2+ medium can be caused by a wide
variety of weak agonists; the secondary aggregation response and release of
granule contents are dependent on TXA2 formation and on feedback
amplification by TXA2 or the prostaglandin endoperoxides. The secondary
responses caused by weak agonists in citrated platelet-rich plasma (which
has a concentration of Ca2+ similar to the low-Ca2+ medium used in the
present studies) do not occur at the concentration of Ca2+ in circulating
blood and thus may have little biologic relevance.
Volume 70,
Issue 3,
pp. 647-651,
09/01/1987
Copyright © 1987 by The American Society of Hematology
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