Interactions of αNi3S2 with Guinea pig alveolar macrophages and liberation of inflammatory mediators

✍ Scribed by E. Teissier; P. Shirali; M. H. Hannothiaux; T. Marez; J. M. Haguenoer

• Book ID: 102872416
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 512 KB
• Volume: 14
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.2550140304

✦ Synopsis

Our previous investigation presented evidence of interaction between aNi3St and membranous and cellular lipids of lung cells, resulting in significant increases in linoleic, linolenic and arachidonic acids. The present work was designed to follow the metabolic fate of arachidonic acid in aNi3S2-exposed guinea pig alveolar macrophages (GPAM) in culture (50 pM aNi3Sz for 3 days). .

The metabolites of arachidonic acid were assessed by HPLC coupled with UV or electrochemical detection. The concentrations of malondialdehyde (MDA), hydroxyeicosatetraenoic acid (HETE), leucotrienes (LT) and reduced glutathione (GSH) were measured.

In exposed cells a significant increase of MDA, a breakdown product of lipid peroxidation, was observed.

In addition, the enzymatic reduction of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) by the associated oxidation of GSH to GSSG increased 5-HETE in GPAM cells and decreased GSH. 5-Hydroperoxyeicosatetraenoic acid was furthermore converted to epoxides, such as leucotriene A4, and we also quantified in exposed cells a signficant increase of its subsequent catabolites LTB,, LTC4 and LTE,.

Direct measurements of MDA and other metabolites of arachidonic acid clearly show that exposure of GPAM cells to aNi3Sz enhances lipid peroxidation. This lipid peroxidation is an autocatalytic free-radical process and could be responsible for DNA damage. Furthermore, aNi& intoxication induces the release of proinflammatory products, such as leucotrienes, and the decrease of glutathione.