Modulation of the free sphingosine levels in human neutrophils by phorbol esters and other factors.

摘要: Because free long-chain bases have been recently found to potent pharmacological effects when added neutrophils (Wilson, E., Olcott, M. C., Bell, R. M., Merrill, A. H., Jr., and Lambeth, J. D. (1986) Biol. Chem. 261, 12616-12623) other cell types, the levels in human were measured by high-performance liquid chromatography. Sphingosine was major base freshly isolated cells ranged from 13 101 pmol/10(7) for different donors (mean +/- S.E. of 50 5, n = 17). Upon incubation at 37 degrees C, there a time-dependent increase sphingosine (57 8% 1 h, 17), but no change seen 4 or 25 C. The apparently derived more complex sphingolipids because little (less than 1%) could be accounted new synthesis [14C]serine. Greater increases obtained incubated with serum, plasma, serum lipoproteins (about 2-fold higher alone). In contrast, agonists such as phorbol 12-myristate 13-acetate, A23187, arachidonic acid, low concentrations (10 nM) N-formyl-methionyl-leucyl-phenylalanine, opsonized zymosan either decreased amount blunted increase. This may due enhanced removal 13-acetate-treated exhibited an increased conversion exogenously [3H]sphinganine ceramides. Endogenous approximately one-tenth level exogenous inhibit protein kinase Hence, depending on subcellular localization endogenous versus bases, amounts might sufficient affect function these cells.