COMPLEMENT ACTIVATION AFTER IN VITRO ASBESTOS EXPOSURE CORRESPONDS TO OXIDANT GENERATION

Abstract

Asbestos exposures are associated with the generation of oxygen-based free radicals. Such oxidants can affect an activation of the alternative complement pathway. This study tested the hypothesis that complement activation after in vitro exposure to asbestos corresponds to the capacity of the fibers to catalyze oxidant generation. After incubation with 1.0 mM H2O2 and 1.0 mM ascorbate, the oxidation of 1.0 mM deoxyribose by 1.0 mg/ml crocidolite was diminished by both the metal chelator deferoxamine (1.0 mM) and the hydroxyl scavenger dimethylthiourea (DMTU) (10.0 mM). Similarly, elevations in [C5b-9] after incubations of plasma with 1.0 mg/ml crocidolite were diminished by inclusion of either 1.0 mM deferoxamine or 10.0 mM DMTU in the reaction mixtures. Pretreatment of crocidolite with deferoxamine to decrease chelatable iron concentrations and the capacity of the dust to generate oxidants resulted in less activation of complement after incubation with plasma. It is concluded that in vitro complement activation by crocidolite is associated with iron-catalyzed oxidant generation by these fibers.