Sulfur mustard toxicity in macrophages: effect of dexamethasone

Cells from the murine macrophage-like cell line J774A.1 (J774) and cultures of primary alveolar macrophages (PAM) obtained from guinea pigs were exposed to sulfur mustard (HD, 50-200 microM) and treated with dexamethasone (2.5 microM) 10 min after HD exposure. Cell cultures were studied at 3 and 24 h after exposure by the cleavage of Thiazolyl blue reaction (MTT) reaction and crystal violet staining (viability assays), by morphological observation and by [3H]thymidine incorporation. Exposure of J774 cells to HD caused a dose-dependent decrease in viability that was evident at 24 h. Although no significant change in viability was observed at 3-4 h after HD exposure, a dose-dependent decrease in [3H]thymidine incorporation was observed. Treatment with dexamethasone caused a dose-dependent decrease in viability. However, the combined exposure to HD and dexamethasone had a synergistic effect on the decrease of cell viability. This synergistic effect is not due to a change in DNA synthesis rate because [3H]thymidine incorporation was not affected by dexamethasone. In PAM cultures, HD caused some 'activating' effect on [3H]thymidine incorporation and an increase in cell number at the lower dose (100 microM) but this was less at 200 microM. Both effects were reduced by dexamethasone treatment. We conclude that macrophages derived from different sources exhibit a different responsiveness to immunomodulators (HD and dexamethasone) and that dexamethasone can reduce the 'inflammatory' effect of HD in PAM.