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Abstract Consequent to asbestos deposition, alveolar macrophages (AM) accumulate at alveolar duct bifurcations where they phagocytize fibers. Because phagocytosis can stimulate the release of arachidonic acid (AA) metabolites, the possibility that secretion of these powerful mediators of inflammation might be induced by chrysotile asbestos was investigated in vitro. Rat AM were treated in vitro with chrysotile asbestos, and the cyclooxygenase products—prostaglandins, thromboxane B2 (TXB2), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT)—and lipoxygenase products—leukotrienes (LT), hydroxyeicosatetraenoic acids (HETE)—secreted in the medium were isolated by high-performance liquid chromatography. Composition of the AA metabolites released was compared with that from those stimulated by the calcium ionophore A 23187 (20 µM) and by another particulate phagocytic stimulus, i.e., carbonyl iron beads. Calcium ionophore stimulation induced a marked release of various AA metabolites in the medium from both the cyclooxygenase pathway (HHT, TXB2, and PGE2, in decreasing quantities, respectively) and the lipoxygenase pathway (LTB4, 5-HETE, 12-HETE, and LTC4). The major product was LTB4. Treatment of the macrophages with asbestos fibers induced the release of a similar array of AA metabolites, although there were smaller amounts of LTC4 and 12-HETE, but increased quantities of PGF2α. A time course study showed a steady increase in metabolite production for 1 h, followed by a plateau. In addition, the amount of metabolites released was dependent on asbestos concentrations. Phagocytosis of iron beads induced the secretion of the same metabolites as asbestos stimulation, but in larger quantities, probably reflecting the lack of cytotoxicity of the particle. Omission of fetal bovine serum during cell adhesion and 3H-AA incorporation in the medium led to a dramatic decrease in the production of cyclooxygenase metabolites after AA metabolism stimulation, although secretion of 12- and 15-HETE was observed after phagocytosis. It appears that the pattern of AA metabolite secretion can be modulated by the presence of serum. Thus, chrysotile asbestos induces a marked stimulation of AA metabolism, with secretion of a wide array of both cyclooxygenase and lipoxygenase metabolites from pulmonary macrophages. This secretion appears nonspecific because phagocytosis of nontoxic carbonyl iron induces the same reactivity.
Kouzan et al. (1985) studied this question.