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Transcellular sulfidopeptide leukotriene biosynthetic capacity of vascular
cells
J Maclouf, RC Murphy and PM Henson
Department of Pharmacology, University of Colorado Health Sciences Center,
Denver 80262.
Cells in the vasculature, including polymorphonuclear leukocytes,
platelets, and endothelial cells, have been shown to be jointly involved in
the biosynthesis of active lipid mediators derived from arachidonic acid.
Stimulation of neutrophils with the calcium ionophore A23187 as a model for
cell activation results in production of leukotriene (LT)A4 with subsequent
intracellular conversion into LTB4. When platelets or endothelial cells
were present in the incubation system, LTC4 was produced from the
neutrophil-derived LTA4. Whereas production and release of LTA4 under
resting conditions in vivo might be expected to be quite low, under
pathologic conditions, LTA4 production could be markedly increased.
Therefore, the metabolism of exogenous LTA4 by platelets and endothelial
cells was studied at a wide range of LTA4 concentrations. The production of
LTC4 during coincubation of neutrophils with platelets was found to be
dependent on neutrophil number ranging from 2 x 10(5) to 2 x 10(7)
cells/mL. When a fixed number of neutrophils were stimulated with platelets
alone or with mixtures of platelets and endothelial cells, LTC4 production
was observed to be dependent on both acceptor cell types. These results
suggest that mixed cell populations, which are likely to occur in vivo, may
be critical determinants of the profile of eicosanoids produced in
pathophysiologic circumstances. We suggest that both endothelial cells and
platelets, in the presence of neutrophils, contribute large quantities of
sulfidopeptide leukotrienes to inflammatory and thrombotic situations.
Furthermore, platelets, because of their quantity and reactivity, may play
a pivotal role in transcellular biosynthesis of eicosanoids.
Volume 74,
Issue 2,
pp. 703-707,
08/01/1989
Copyright © 1989 by The American Society of Hematology
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