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

Abstract

We investigated the susceptibility of peritoneal mouse macrophages and macrophage and microglia cell lines to the peroxidative activity of [~-haematin, the synthetic polymer identical to native malaria pigment. The extent of lipid peroxidation, measured as production of thiobarbituric acid reactive substances (TBARS), was greater for peritoneal macrophages than for cell lines and microglia cells. TBARS production apparently was not attributable to the release of free iron from the protoporphyrin moiety, but related to lower glutathione content and different lipid composition of the cell membrane. These findings offer a new interpretation for the contentious immunomodulatory effects of [~-haematin reported for phagocytes of different origins.© 1998 Federation of European Biochemical Societies.Key words: Macrophage; [3-Hematin; Malaria pigment; Lipid peroxidation tathione [ll]. These findings suggest the involvement of oxidative mechanisms in the intracellular activity of [~-haematin, due to the known properties of haem-containing molecules as catalysts of lipid peroxidation [12]. This prompted us to verify whether (i) [3-haematin has prooxidant activity in macrophages and (ii) the ability of the different macrophage populations to cope with the [3-haematin-induced oxidative stress is related to a different membrane lipid composition and/or to the level of antioxidant defences. Materials and methods MiceSpecific pathogen-free female CD1 mice, 6-8 weeks old, were obtained from Charles River Italia (Calco, Como, Italy). Mice were maintained under conventional conditions and fed standard mouse pellet and water ad libitum.

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

“…Although we cannot rule out the possibility that the increased HO-1 expression may be a direct effect of the heme moiety of BH, the results presented in Figure 2, along with the finding that the effect of BH on nitrite production was prevented by reducing agents, suggest that HO-1 up-regulation is caused by BH-induced oxidative injury. This conclusion is in agreement with the increased levels of lipid peroxidation induced by malaria pigment in human monocytes (Arese and Schwarzer, 1997) and mouse macrophages (Omodeo-Salè et al, 1998). In view of these considerations, it is difficult to reconcile our results with recent reports of the lack of induction of HO-1 in hemozoin-fed human monocytes (Schwarzer et al, 1999) that had been shown to experience oxidative stress upon ingestion of hemozoin (Schwarzer et al, 1992).…”

“…Because the two cell types ingested BH to a similar extent (Taramelli et al, 1995), the lower response to oxidant stress cannot be attributed to a different accumulation of pigment and is likely to depend on the cell's antioxidant status. In fact, BV2 cells have a lower content of unsaturated membrane fatty acids and higher levels of reduced glutathione (GSH) levels, both indicative of reduced sensitivity to oxidant stress (Omodeo-Salè et al, 1998). …”

Accelerated senescence of human erythrocytes cultured with Plasmodium falciparum

“…Even hemozoin that is considered a nontoxic storage of heme for the parasites has been shown to catalyze peroxidative processes in cell culture and cell-free systems. 10,11,51 Parasites seem to use different tools to cope with such an environment: (1) they are rich in antioxidant enzymes either imported from host or newly synthesized; (2) as shown here, the composition of their membranes is quite resistant to oxidative damage; and (3) to minimize contact with oxygen, they have evolved a way to survive in microaerophilic conditions. The food vacuole, the organelle where the digestion of hemoglobin occurs, is likely to be an anaerobic compartment, as we recently suggested.…”

“…We reasoned that a better knowledge of the lipid composition of trophozoites membranes would help in solving the paradox of parasites, which grow in an iron-porphyrin rich environment, accumulating hemozoin that is toxic for host membranes 10,11 and yet survive.…”

Phagocytosis of Hemozoin (Native and Synthetic Malaria Pigment), and Plasmodium falciparum Intraerythrocyte-Stage Parasites by Human and Mouse Phagocytes

“…A murine macrophage-like cell line (J774) [20] was maintained in MEM (Gibco-BRL-Life technologies) supplemented with 10% heatinactivated FBS (HyClone), 1% glutammine, 1% non-essential amino acid, 2% tricine and 1% penicillin-streptomycin in 5% at 37°C. J774 CO2 macrophages were mechanically collected with a cell lifter (Costar Italia, Milan, Italy) and transferred to a fresh medium every 3± 4 days.…”