Regulation of leukotriene synthesis by arachidonic acid in human polymorphonuclear leukocyte adhesive interactions is dependent on the presence of albumin.
We have previously demonstrated that the pretreatment of polymorphonuclear leukocytes (PMNs) with the chemotherapeutic drug, Suramin, increases both cell attachment and inhibits calcium ionophore A23187-stimulated leukotriene (LT) synthesis. Here, we examined the effects of extracellular arachidonic acid (AA) and albumin on attachment and LT synthesis in the interaction of PMNs with both collagen-coated surfaces and human umbilical vein endothelial cell (HUVEC) monolayers. Suramin decreased the release of radiolabelled AA and 5-lipoxygenase metabolites by [(14)C-AA]-prelabelled PMNs stimulated with A23187, with and without human serum albumin (HSA) in the culture medium. Addition of 1 microM AA together with calcium ionophore stimulated the release of endogenous AA to the same level as control and Suramin-pretreated cells, but attachment was unaffected and LT synthesis was still inhibited with Suramin treatment. Using 24 microM AA, regulation of LT synthesis was dependent on the presence of HSA in the medium. Without HSA, 24 microM AA induced detachment of PMNs and increased LT synthesis in Suramin-treated cells above the control level. In the presence of HSA, 24 microM AA did not influence PMN attachment or abolish Suramin-induced inhibition of LT synthesis. These results suggest that tight attachment of PMNs to a solid surface leads to decreased LT synthesis during subsequent stimulation of the cells by A23187 in the presence or absence of exogenous substrate.
Pushkareva
Marina A
MA
A N Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119992, Russia.
Turutin
Denis V
DV
Sud'ina
Galina F
GF
D016718:Arachidonic Acid / Q000494:pharmacology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D012709:Serum Albumin / Q000502:physiology*
D015289:Leukotrienes; D012709:Serum Albumin; D016718:Arachidonic Acid