The Heme Moiety of Malaria Pigment (β-Hematin) Mediates the Inhibition of Nitric Oxide and Tumor Necrosis Factor-α Production by Lipopolysaccharide-Stimulated Macrophages

Macrophage populations of different origins have distinct susceptibilities to lipid peroxidation induced by β‐haematin (malaria pigment)

“…Peritoneal exudate macrophages, J774.1 macrophage like cells and BV2 microglial cells proved able to readily ingest I3-haematin: intracellular pigment could be detected at the end of the 4-h treatment in 75 80% of the cells, as confirmed by light and electron microscopy [11]. The extent of pbagocy-…”

“…We had already reported that treatment of peritoneal macrophages with ]3-haematin results in impaired macrophage functions, and that the inhibition of NO and TNFc~ production by [3-haematin-treated peritoneal macrophages is partially counterbalanced by the addition of sulphydryl group donors or glutathione [11].…”

“…For the lipoperoxidation experiments, cells were seeded at 5-6 x 10~/ml and treated for 4 h with [3-haematin or soluble haematin (51) gg/ml) or cultured in CM only. Cell viability was assessed by trypan blue exclusion and metabolic activity [11]. Cell homogenate was prepared by subjecting cell suspension to two cycles of freezing-thawing followed by a brief sonication and total protein content was determined according to Smith [15].…”

“…Repeated cycles of phagocytosis as well as the production of oxygen radicals and nitrogen oxides are inhibited [7,8]. In addition, we also showed that peritoneal mouse macrophages fed with [3-haematin, a synthetic polymer of Fe(III)-PPIX identical to native haemozoin [9,10] failed to produce TNFcx and Nitric Oxide (NO) when stimulated by lipopolysaccharide (LPS) [11]. Two aspects of this phenomenon are worth noting: (i) by contrast to peritoneal macrophages, microglia cells derived fi'om the same mouse strain proved quite refractory to the [3-haematininduced functional inhibition; (ii) the inhibition of NO and TNFc~ production observed in peritoneal macrophages was partially counterbalanced by the addition of sulphydryl group donors such as 2-mercaptoethanol, N-acetylcysteine and glu-*Corresponding author.…”

Macrophage Preconditioning with Synthetic Malaria Pigment Reduces Cytokine Production via Heme Iron-Dependent Oxidative Stress

“…Although a clinical correlation between the presence of pigment in circulating neutrophils and monocytes and disease severity is established (Nguyen et al, 1995), the nature of the interaction between pigment and phagocytes, as well as its contribution to the pathogenesis of malaria, and particularly its severe complications, are still controversial. Indeed, both pro-inflammatory (induction of tumor necrosis factor ␣ [TNF␣], interleukin-6 [IL-6], and chemotactic cytokines) (Pichyangkul et al, 1994;Prada et al, 1995;Sherry et al, 1995) and antiinflammatory activities (inhibition of respiratory burst and adhesion molecule expression and of TNF␣ and nitric oxide [NO] production) (Prada et al, 1995;Schwarzer et al, 1992;Taramelli et al, 1995Taramelli et al, , 1998 have been described in pigment-fed phagocytes. The study of such interactions is simplified now by the availability of ␤-hematin (BH), a synthetic polymer obtained from hematin in acidic conditions.…”