Modulation of peripheral blood mononuclear cell cyclic adenosine monophosphate levels by human very low density lipoprotein

Abstract

Normal human plasma very low density lipoprotein (VLDL) can inhibit mitogen-induced lymphocyte DNA synthesis. Since early events in lymphocyte activation (e.g., cyclic nucleotide metabolism) are thought to influence the magnitude of later events (e.g., [ 3H]thymidine uptake) we designed the current studies to compare the effects of VLDL on these two cellular processes. Two separate effects of VLDL on peripheral blood mononuclear cell (PBM) cyclic adenosine monophosphate (AMP) metabolism were observed at VLDL concentrations which inhibit phytohemagglutinin (PHA)-induced [ 3H]thymidine uptake. VLDL suppressed the early, transient increase in PBM cyclic AMP which occurs within minutes of the addition of mitogen. VLDL exposure also stimulated a delayed (greater than 24 hr) and spontaneous increase in PBM cyclic AMP levels which corresponded temporally with progressive cellular refractoriness to mitogen stimulation. If mitogen-induced lymphoproliferation is influenced by early changes in cyclic nucleotide metabolism, as claimed by some investigators, then perhaps the ability of VLDL to modulate intracellular cyclic AMP levels may explain some of the antiproliferative properties of this bioregulatory lipoprotein.