ROLE OF MONOCYTES AND INTERSTITIAL-CELLS IN THE GENERATION OF ALVEOLAR MACROPHAGES .1. KINETIC-STUDIES OF NORMAL MICE

Abstract

Following monocytic depletion, alveolar macrophages are produced by a local cell renewal system within the pulmonary interstitium. Contributions of hematopoietic and interstitial components to the output of macrophages in the normal state is unknown. In the present autoradiographic study, sequential labeling and grain counts in monocytes, interstitial cells and free alveolar macrophages were examined in mice up to 7 wk after 3 injections of 3H-thymidine; the animals also received colchicine 4 h before sacrifice. Labeling patterns of interstitial cells and macrophages were biphasic. The initial peaks with very few mitotic figures were consistent with migration of blood monocytes across the interstitium to the alveoli. In the 2nd phase, when no labeled monocytes were present, a few heavily labeled macrophages were observed up to 7 wk; in this period mitoses and heavy labeling were seen in a few interstitial mononuclear cells. Under normal circumstances the predominant mechanism of macrophage production is apparently direct passage of monocytes across the interstitium to the alveoli. This may be rapid at the thin-walled capillaries and take up to 2 days where the interstitium is thicker. A smaller proportion of cells appears to arise by division of resident interstitial cells with subsequent migration to the alveoli. The sojourn of free macrophages in the alveolus under basal conditions is 7 days.