Role of monocytes and interstitial cells in the generation of alveolar macrophages II. Kinetic studies after carbon loading.

Increased production of alveolar macrophages after carbon administration to the lung is biphasic; initially the increase is unrelated to cell division in the lung, whereas later, mitotic activity is observed in the interstitium. The role of monocytes and interstitial cells in this dual response is now investigated by injecting 3H-thymidine 1 day before administering 4 mg. of carbon to mice, and following the sequential labeling and grain counts of monocytes, interstitial cells, and free alveolar macrophages. The mice also received colchicine 4 hours before sacrifice. The results suggest that the half life of circulating monocytes is reduced after carbon, indicating that more rapid monocyte production in the marrow is balanced by faster migration from the blood. The kinetic data also suggest that increased cellularity of the interstitium in response to carbon is related initially to monocytic passage from blood to alveoli, and later is associated with division of interstitial cells. The slight increase in mitotic activity observed in alveolar macrophages is not sufficient to account for the large increase in free cells. It is concluded that the adaptive outpouring of macrophages following carbon is an acceleration of the normal dual mechanism whereby most cells are derived from monocytes crossing the interstitium without division and a smaller proportion arising by division of interstitial cells with migration to the alveoli.