Adaptive responses of the pulmonary macrophagic system to carbon. I. Kinetic studies

The adaptive capacity of the lung to increase the output of alveolar macrophages is vital to its handling of foreign material, particularly in an overload situation. In previous papers we demonstrated the role of pulmonary intersititial cells in providing a pool of precursor cells that may be available for this purpose. We now extend these observations to a study of pulmonary cytodynamics in mice subjected to a single large load (4 mg.) of carbon delivered by endotracheal tube. The output of free macrophages over a period of 14 days was correlated with DNA synthesis of pulmonary cells as measured by their uptake of 3H-thymidine. The initial increase of macrophagic output, 5 times in 12 hours and 10 times in 24 hours occurred before any increase in mitotic activity or cellularity was demonstrated in the pulmonary interstitium. The high level of macrophagic cell output which was maintained over the next week was accompanied by increased thymidine uptake in the lung. Increased mitotic activity was confined to the interstitial cell population; no mitoses were observed in free macrophages. The results indicate a biphasic macrophagic response to inhaled particulates, an early phase apparently unrelated to a local cellular response and a later phase of interstitial cell proliferation which appears to be concerned with the maintenance of the high output of macrophages.