ALVEOLAR MACROPHAGE RESPONSE TO CARBON IN MONOCYTE-DEPLETED MICE

Abstract
The predominant source of alveolar macrophages is monocytic migration, with a smaller proportion arising from dividing interstitial cells. To determine how this system responds to particulate loading when depleted of monocytes, mice received 650 rad whole-body irradiation followed by 4 mg C instilled into the trachea. Control groups included irradiated mice given no C and nonirradiated mice given C. After irradiation alone, the number of monocytes fell to a low level for at least 3 wk, whereas the output of alveolar macrophages remained normal. In nonirradiated mice, C induced a 10-fold increase in macrophages in the 1st day, dropping rapidly after 1 wk. Macrophage output in irradiated animals given C doubled the 1st day, when rose to 4 times normal after 2 wk. This limited response to C was accompanied by increased DNA synthesis in pulmonary interstitial cells, but the number of circulating monocytes and labeling of alveolar macrophages remained very low. When monocytes are not available, output of alveolar macrophages is maintained by precursor cells in the pulmonary interstitium. This interstitial compartment provides an essential back-up mechanism capable of responding to increased particulate loading in both normal and monocytopenic animals.