Immunocytochemical characterization of lung macrophage surface phenotypes and expression of cytokines in acute experimental silicosis in mice

The expression of the surface phenotypical profile and the cytokines TNF-al pha and IL-1 beta from murine lung macrophages was studied in parenchymal l ung tissue and bronchoalveolar fluid of mice, over a 2-week period, followi ng a single intratracheal instillation of silica. The acute inflammatory re action, confirmed by a significant augmentation of four times the control v alues of the number of macrophages recovered by lavage from experimental an imals, was followed by organized granulomas in the interstitium. The immuno histochemical analysis of lung tissue sections after silica instillation de monstrated the increased alveolar and interstitial tissue expression of all surface antigens and cytokines studied, mainly Mac-1, F4/80 antigens, TNF- alpha and IL-1 beta, which were occasionally observed in normal uninjected and saline-treated mice. These findings show that, after silica instillatio n, the expression of surface phenotypical markers of lung macrophages incre ased, and this change was concomitantly associated with an increased expres sion of the cytokines TNF-alpha and IL-1 beta. These changes support the co nclusion that an influx of the newly recruited and activated macrophage pop ulation, with a different phenotype, is induced by treatment during inflamm ation. The populational changes involve difference in functional activity a nd enhance TNF-alpha and IL-1 beta expression. These cytokines, produced in the silicosis-induced inflammatory process, are associated with the develo pment of fibrosis and may contribute to disease severity. (C) 1998 Chapman & Hall.