INCREASED LEVELS OF 4-HYDROXYNONENAL IN HUMAN MONOCYTES FED WITH MALARIAL PIGMENT HEMOZOIN - A POSSIBLE CLUE FOR HEMOZOIN TOXICITY

In human monocytes, lipoperoxides were increased 3-fold at 2 h, 6-fold at 5 h and 7.5-fold at 12 h after hemozoin phagocytosis, 4-Hydroxynon enal (HNE) was also increased, reaching 40 nmol/10(10) cells at 2 h (a pproximate intracellular concentration [AIE] 8 mu M), 230 nmol/10(10) cells at 5 h (ALE 46 mu M) and 79 nmol/10(10) cells (AIE 16 mu M) at 1 2 h. A moderate increase in HNE, approx, 20 nmol/10(10) cells (AIE 4 m u M) was also observed after phagocytosis of anti-D IgG-opsonized eryt hrocytes, HNE in unfed controls was approx, 5 nmol/10(10) cells (AIE 1 mu M) during the whole incubation period, An increased amount of prot ein kinase C (PKC)/HNE adduct was demonstrated in hemozoin-fed monocyt es, Purified PKC was profoundly inhibited at HNE > 10 mu M The impairm ent of PI(C previously observed in hemozoin-fed monocytes can thus be explained by direct interaction with increased HNE levels.