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-Hydroxynonenal (HNE) was also increased, reaching 40 nmol/10(10) cells at 2 h (approximate intracellular concentration [AIE] 8 microM) 230 nmol/10(10) cells at 5 h (AIE 46 microM) and 79 nmol/10(10) cells (AIE 16 microM) at 12 h. A moderate increase in HNE, approx. 20 nmol/10(10) cells (AIE 4 microM) was also observed after phagocytosis of anti-D IgG-opsonized erythrocytes. HNE in unfed controls was approx. 5 nmol/10(10) cells (AIE 1 microM) during the whole incubation period. An increased amount of protein kinase C (PKC)/HNE adduct was demonstrated in hemozoin-fed monocytes. Purified PKC was profoundly inhibited at HNE > 10 microM. The impairment of PKC previously observed in hemozoin-fed monocytes can thus be explained by direct interaction with increased HNE levels.