Increased levels of 4‐hydroxynonenal in human monocytes fed with malarial pigment hemozoin A possible clue for hemozoin toxicity

Abstract
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/1010 cells at 2 h (approximate intracellular concentration [AIE] 8 μM), 230 nmol/1010 cells at 5 h (AIE 46 μM) and 79 nmol/1010 cells (AIE 16 μM) at 12 h. A moderate increase in HNE, approx. 20 nmol/1010 cells (AIE 4 μM) was also observed after phagocytosis of anti‐D IgG‐opsonized erythrocytes. HNE in unfed controls was approx. 5 nmol/1010 cells (AIE 1 μM) 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 μM. The impairment of PKC previously observed in hemozoin‐fed monocytes can thus be explained by direct interaction with increased HNE levels.

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