REGULATORY EFFECTS OF LIPOPROTEIN-LIPASE ON PROLIFERATIVE AND CYTOTOXIC ACTIVITY OF NK CELLS

Lipoprotein lipase (LPL) induced, in a dose-dependent fashion, a 2-fol d and 11-fold increase in the proliferative response of peripheral blo od lymphocytes (PBL) at 48 and 72 h, respectively; a 4- and 12-fold in crease in natural killer (NK) cells, respectively; and a maximal 3-fol d induction in interleukin-2 (IL-2)-treated NK cells at 72 h. T lympho cytes did not proliferate independently of the concentration of LPL us ed. LPL decreased the proliferative response of K562 and U937 cell lin es. The effect on NK cells could be blocked by anti-LPL if it was adde d before LPL binding to the cell membrane. Contrary to its effects on NK proliferative response, LPL inhibited spontaneous cytotoxicity and lymphokine-activated killer activity (LAK). The effect was dose-depend ent, target-dependent (U937 was more sensitive than K562 in Wt assays) , but not LPL-binding time-dependent. Treatment of NK cells with hepar inase overcame the inhibitory effect of LPL in spontaneous cytotoxicit y. LPL binding to cell membranes, as assessed by flow cytometry, was a s follows: K562 cells > monocytes > NK cells > Wt cells > U937 cells, absent in T lymphocytes and partially sensible to heparinase and IL-2 treatments. Protein kinase C translocation was observed upon treatment of NK cells with LPL. Three proteins in NK cell membrane (76, 57.2, a nd 27.2 kD), two in the cytosol (57.2 and 27.2 kD), and only one in AN A-1 cell membrane (76 kD) were precipitated with LPL-Sepharose. LPL re ceptors seem to be responsible for the proliferative and cytotoxic res ponse observed in LPL-stimulated NK cells.