No abstract

Alveolar macrophages are thought to arise from both marrow-derived monocytes and pulmonary interstitial cells. Macrophage kinetics are now studied under various conditions of alveolar loading using several doses of carbon (0.03 micrometers diameter), polystyrene latex (0.1 and 1.0 micrometers), and heat-killed bacteria. In serial studies we examined the number of macrophages recovered by lavage, DNA synthesis by lung cells on autoradiographs, and the passage of free particles into lung tissues by electron microscopy. The dual origin of the alveolar macrophage was confirmed for each particulate. The observed peak in macrophagic output at 1 day may be explained by monocytic egress. With greater loads, the peak value did not increase, but the continuing macrophagic production correlated with a period of interstitial cell proliferation. For all particles used, the number of new macrophages was related more closely to number of particles instilled than to the total dose by weight delivered to the lungs. With increasing number, more free particles of carbon and latex crossed the Type 1 epithelium to be phagocytized by interstitial macrophages. The results suggest that the adaptive outpouring of alveolar macrophages occurs by an acceleration of the normal biphasic pathway; when the adaptive response is prolonged, the interstitial compartment appears to be the predominant source of new cells.

No abstract

To determine the cellular and fibrogenic responses of the lung to long asbestos fibres, mice were instilled intratracheally with 0.1 mg of a sample of long crocidolite fibres. Animals were killed at intervals to 20 weeks with 3H thymidine injected one h before death. Following bronchoalveolar lavage, an increase in polymorph neutrophils (PMN) and alveolar macrophages (AM) was found during the first week, accompanied by elevated glucosaminidase and alveolar protein levels. Although the PMN number dropped, some were always recovered by lavage to 20 weeks. Early multifocal necrosis of bronchiolar epithelium was followed by a large increase in labelling of epithelial cells and underlying fibroblasts. Epithelial overgrowth of luminal long fibres and inflammatory exudates was followed by giant cell and granuloma formation in the interstitium. After four weeks collagen levels were significantly increased and fibrosis was seen in these peribronchiolar locations. A few small fibres were observed in AM but no evidence of fibrosis was seen in alveolar walls. These findings suggest that injury to bronchial and bronchiolar epithelium allows long fibres to reach the interstitium where subsequent macrophage-fibroblast interactions result in a severe fibrotic reaction that resembles the bronchiolar component of human asbestosis.

The pathogenesis of silicosis involves interaction between pulmonary macrophages and fibroblasts. The consequences of direct injury to pulmonary cells and the role of inflammatory cells other than the macrophage have received little attention. These were studied over a 20 week period after instilling silica to mice by correlating the changing inflammatory response, as revealed by bronchoalveolar lavage and lung sections, with the cellular location of silica particles and the development and resolution of granulomatous lesions. Within 24 h, a massive concentration of particles and PMN was seen in centrilobular locations with acute focal necrosis of type 1 epithelial cells. Rapid epithelial repair occurred but PMN were recovered from the lung up to 20 weeks. In the alveoli, silica was ingested by PMN and AM, resulting in the death of some cells; free particles crossed the epithelium and were found predominantly in peribronchial macrophages. Silicotic granulomas formed within a week and consisted mainly of fibroblasts macrophages and some PMN. It is suggested that the necrosis of type 1 epithelium and the continuing efflux with serial destruction of PMN may be important factors in the generation of silicotic fibrosis.