Journal of Lipid Research, Vol 25, 1195-1205, Copyright © 1984 by Lipid Research, Inc.
The phosphatidylinositol response and proliferation of oxidative enzyme- activated human T lymphocytes: suppression by plasma lipoproteins
AL Akeson, DW Scupham and JA Harmony
The phosphatidylinositol (PI) response and DNA synthesis of neuraminidase
and galactose oxidase (NAGO)-stimulated human T lymphocytes are suppressed
by low density lipoproteins (LDL). To understand the mechanism of
lymphocyte activation more fully, the PI response and DNA synthesis and
suppression of these events by LDL in NAGO-stimulated T lymphocytes were
characterized. Between 30 min and 6 hr after NAGO stimulation, there was an
increase of 32Pi incorporation into PI without increased incorporation into
the phosphorylated forms of PI or into other phospholipids. DNA synthesis
as determined by [3H]thymidine incorporation depended on the
lymphocyte-accessory monocyte ratio and total cell density. Optimal
stimulation of the PI response and DNA synthesis occurred at the same
concentration of neuraminidase and galactose oxidase. While the PI response
was only partially suppressed by LDL with optimal suppression at 10 to 20
micrograms of protein/ml, DNA synthesis was completely suppressed although
at much higher LDL concentrations, greater than 100 micrograms protein/ml.
As monocyte numbers are increased, LDL suppression of DNA synthesis is
decreased. The ability of NAGO to stimulate the PI response and DNA
synthesis in a similar way, and the suppression of both events by LDL,
suggests the PI response is important for lymphocyte activation and
proliferation. Stimulation of human T lymphocytes by oxidative mitogens,
neuraminidase, and galactose oxidase caused increased phosphatidylinositol
metabolism and increased DNA synthesis. Both responses were suppressed by
low density lipoproteins.
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