Immunomodulation in mineral dust-exposed lungs: stimulatory effect and interleukin-1 release by neutrophils from quartz-elicited alveolitis. |
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| Authors: | Y Kusaka R T Cullen K Donaldson |
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| Affiliation: | Institute of Occupational Medicine, Edinburgh, Scotland. |
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| Abstract: | Quartz deposition in the rat lung causes an intense and persistent neutrophil alveolitis leading to parenchymal fibrosis. Bronchoalveolar leucocytes (BAL) from quartz-exposed rat lungs were studied for their effects on splenic lymphocyte proliferation; titanium dioxide (TiO2) was used as a control, non-fibrogenic dust. Seven days after the intratracheal instillation of 1 mg of quartz or TiO2 suspended in phosphate-buffered saline (PBS), BAL were recovered by lavage; the effect of PBS alone was also studied. TiO2-elicited BAL (macrophages greater than 98%) inhibited splenocytes responding to suboptimal phytohaemagglutinin (PHA) more than PBS-elicited BAL (macrophages greater than 98%); the effect was dependent on the BAL:splenic lymphocyte ratio. Quartz-elicited whole BAL (macrophages 49%, neutrophils 51%), and an alveolar macrophage-enriched population with purity of 87% separated from it, were less inhibitory to splenocyte mitogenesis than PBS-elicited BAL. A neutrophil-enriched population, with a purity of 80%, markedly enhanced splenocyte response to PHA. In addition, whole quartz BAL and the macrophage-enriched population obtained from it enhanced the mitogenesis of T cell-enriched lymphocytes at a much lower BAL:lymphocyte ratio. The neutrophil-enriched quartz BAL enhanced mitogenesis substantially more than the whole or macrophage-enriched population from quartz-exposed lung. Supernatants from normal macrophages, PBS BAL, TiO2 BAL, quartz BAL and both alveolar macrophage and neutrophil-enriched quartz populations were assessed for interleukin-1 (IL-1) activity. Quartz-BAL, quartz macrophages and quartz neutrophils all produced significantly higher IL-1 levels than PBS BAL; the supernatants from quartz neutrophils, however, showed the highest IL-1 activity. These findings suggest that quartz-elicited bronchoalveolar leukocytes, especially neutrophils, enhance lymphocyte proliferation and that increased IL-1 secretion by these cells is likely to be the effector molecule involved. These findings have important implications for immune response in mineral dust-stimulated lung and for inflammatory lung disease in general. |
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| Keywords: | immunomodulation lungs quartz macrophages neutrophils |
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