Immunoregulatory Properties of Human Plasma in Very Low Density Lipoproteins

Abstract

Physiologic concentrations of VLDL isolated from human plasma by ultracentrifugal flotation and molecular exclusion chromatography inhibit the induction of DNA synthesis in human PBM by a variety of mitogenic and allogeneic cell stimuli. Rapid inhibition of PHA responsiveness during a brief (1 hr) VLDL pulse suggests a high affinity interaction between the inhibitor and its target cell(s) with rapid translation of the inhibitory message to intracellular sites responsible for the initiation of DNA synthesis. PBM refractoriness to VLDL when administered later than 6 to 12 hr after PHA suggests that early, inductive events in the DNA synthesis response of PBM of mitogens are susceptible to modulation by this inhibitor. Currently demonstrated inhibition of protein synthesis and previously documented inhibition of sterol metabolism by VLDL suggest that suppression of the DNA synthetic response of PBM might be mediated by one or both of these early prereplicative events. The VLDL employed in these studies were shown to be free of the previously described inhibitory species of LDL (LDL-In) and were characterized by a variety of physicochemical, biochemical, and immunochemical parameters virtually incompatible with the other inhibitors of PBM DNA synthesis known to occur in human plasma. Considerable presumptive evidence suggests that inhibition depends on the biologic expression of the apolipopeptide B moiety which VLDL share with the bioregulatory low density lipoproteins and that VLDL may represent the physiologic progenitor of these molecules. The current studies clearly add VLDL to the enlarging family of immunoregulatory lipoproteins biologically active as subphysiologic concentrations and therefore potentially important in the continuing maintenance of immunologic homeostasis. The precise role played by these molecules in the preservation of human immunologic integrity remains to be determined.