Maryse Beraud

Double-walled carbon nanotubes trigger IL-1β release in human monocytes through Nlrp3 inflammasome activation.

Because of their outstanding physical properties, carbon nanotubes (CNTs) are promising new materials in the field of nanotechnology. It is therefore imperative to assess their adverse effects on human health. Monocytes/macrophages that recognize and eliminate the inert particles constitute the main target of CNTs. In this article, we report our finding that double-walled CNTs (DWCNTs) synergize with Toll-like receptor agonists to enhance IL-1β release in human monocytes. We show that DWCNTs-induced IL-1β secretion is exclusively linked to caspase-1 and to Nlrp3 inflammasome activation in human monocytes. We also establish that this activation requires DWCNTs phagocytosis and potassium efflux, but not reactive oxygen specied (ROS) generation. Moreover, inhibition of lysosomal acidification or cathepsin-B activation reduces DWCNT-induced IL-1β secretion, suggesting that Nlrp3 inflammasome activation occurs via lysosomal destabilization. Thus, DWCNTs present a health hazard due to their capacity to activate Nlrp3 inflammasome, recalling the inflammation caused by asbestos and hence demonstrating that they should be used with caution.

[1-14C]Arachidonic acid incorporation into glycerolipids and prostaglandin synthesis in peritoneal macrophages: effect of chloramphenicol.

Peritoneal macrophages from normal mice were labelled with [1-14C]arachidonic acid after 2 h culture. The uptake of arachidonic acid into cellular lipids was rapid, time-dependent and can be represented within the limit of the studied times by a parabolic regression. Indomethacin decreased the kinetics of uptake; this inhibition is dose-dependent. Chloramphenicol had no effect on macrophage [1-14C]arachidonic acid uptake. After 3 h, the radioactivity was recovered in phosphatidylcholine (38.6%), phosphatidylserine-phosphatidylinositol (8.5%), phosphatidylethanolamine (22.1%), diacylglycerol (2.9%), triacyglycerol (2%) and cholesteryl ester (11.8%). Chloramphenicol and indomethacin inhibited the labelling of phospholipids and stimulated the labelling of neutral lipids and cholesteryl ester. Studies on arachidonic acid release from glycerolipids of prelabelled 2-h cultured macrophages showed that phosphatidylcholine and phosphatidylserine-phosphatidylinositol are the major source of arachidonic acid in prostaglandin synthesis in macrophages stimulated or not by zymosan. Chloramphenicol inhibited release of fatty acid from phosphatidylcholine and phosphatidylserine-phosphatidylinositol; indomethacin had no effect. Both drugs inhibited prostaglandin synthesis in stimulated or non-stimulated macrophages. In the culture medium, indomethacin increased the release of free arachidonic acid by stimulated macrophages. Possible explanations for the mechanisms underlying these effects are presented. It is concluded that indomethacin and chloramphenicol exert profound effects on the metabolism of phospholipids and its zymosan activation. Chloramphenicol appears to impair prostaglandin synthesis through several mechanisms and especially through phospholipase inhibition.

Chemiluminescence response and arachidonic acid metabolism of macrophages induced by γ-hexachlorocyclohexane (lindane).

The influence of gamma-hexachlorocyclohexane (gamma-HCCH) on arachidonic acid (AA) metabolism and oxygen metabolite production was investigated on mouse peritoneal macrophages gamma-HCCH stimulated 6KPGF1 alpha, PGE2, LTC4, LTB4 and HETEs production and increased the luminol-dependent chemiluminescence (CL). Lindane acted synergistically with phorbol ester on prostaglandins-leukotrienes (PGs-LTs) and CL production. Similar stimulation of CL and PGs-LTs production was found after challenge by the calcium ionophore A23187. The implication of calcium mobilization in lindane effects was proposed.

The effects of locally injected antibiotic on carrageenan-induced granuloma in rats

Indomethacin (0.5 mg/100 g b.w./day) and chloramphenicol (0.5 mg or 15 mg/100 g b.w./day) were tested for their anti-inflammatory effects on 7th day carrageenan-induced granuloma formation. Neither of the drugs modified granuloma or pouch wall weight but they decreased the exudate and the cluster of dead cells. Indomethacin and chloramphenicol decreased glucosamine in the dead cell granuloma fraction and increased the level of collagen in the pouch wall. The drugs differed in their inhibitory effect on lysozyme and prostaglandin E2 accumulation in the exudate. The increase in collagen was related to a drop in the level of prostaglandin E2 which seems to regulate collagen deposition in the granuloma. However, the prostaglandin E2-lysozyme correlation--which was only significant with chloramphenicol--suggests a mode of action for chloramphenicol different from that of indomethacin. Chloramphenicol could act by a myelodepressive and/or chemotactic effect. The effects of chloramphenicol on the macrophages are discussed.

Distribution of radioactivity following oral administration of carcinogenic 14CH3-labelled nitrosocarbaryl in the rat

After a single intragastric administration of 14C-labelled carcinogenic nitrosocarbaryl, a nitrosated pesticide, the distribution of radioactivity was investigated in the blood and a number of organs in male rats. The animals received 0.25 mg/kg of labelled nitrosamine and were killed following administration at timed intervals between 0.5 h and 24 h. Our results show that the greatest amount of the 14CH3--group was associated with the forestomach, tumor-susceptible tissue; the level of radioactivity is noteworthy but less important in the glandular stomach. There are also sites of radioactivity accumulation mainly in the liver. Moreover, [14C]nitrosocarbaryl was revealed in the blood suggesting that nitrosamine itself rapidly (0.5 h) crosses the intestinal barrier and in a significant quantity (13%). These facts constitute a potential carcinogenic risk.

Relations entre la structure chimique de quinoxalines disubstituees en positions 2,3 et les activites de detoxication enzymatique des microsomes hepatiques du rat

Abstract The effects of some 2,3 disubstituted quinoxalines on rat liver microsomal cytochrome P-450, aniline aromatic hydroxylation. p -nitroanisole O -demethylation. aminopyrine and N -methylaniline N -demethylations were studied. Pretreatments of female rats with quinoxaline, 2,3-dimethylquinoxaline and 2,3-diphenylquinoxaline, intraperitoneally for 4 days (50 mg/kg/day) increased the metabolic rates of some but not all of the four reactions. Whereas. 2,3-dithiolquinoxaline inhibited the O -demethylation of p -nitroanisole and decreased the cytochrome P-450 per mg microsomal protein; 2,3-dichloroquinoxaline, 2,3-dihydroxyquinoxaline and 2-hydroxy, 3-methylquinoxaline had no effect. These results suggested a correlation between microsomal activity and physicochemical characters of quinoxaline derivatives.