Activation of Rat Alveolar Macrophages to the Tumoricidal State in the Presence of Progressively Growing Pulmonary Metastases¹

The purpose of this study was to determine whether the presence of progressively growing pulmonary metastases influences the number and function of alveolar macrophages (AM). Female F344 rats were given i.v. injections of cells from a metastatic variant line of the syngeneic adenocarcinoma MADB-105. At Days 7, 14, 21, and 28 after injection, normal and tumor-bearing animals (3/group) were killed, and their AM were harvested by lavage. The functional integrity of AM was determined by their capacity to phagocytose opsonized erythrocytes and by their ability to respond to a variety of activating agents in vitro. Normal and metastasis-bearing rats were given i.v. injections of Nocardia rubra cell wall skeleton to determine whether the presence of large pulmonary metastases would interfere with AM activation in situ. The data demonstrated that the presence of progressively growing lung metastases led to a slight increase in the number of harvested AM and that these cells from tumor-bearing rats were as phagocytic as AM obtained from normal rats. Also, AM harvested from rats with metastases became tumoricidal against syngeneic tumor target cells in response to activation stimuli in vitro and in vivo.

We conclude that, in this tumor system, the presence of progressively growing lung metastases does not suppress the number or function of AM. The use of agents known to activate AM could, therefore, be of benefit in the therapy of pulmonary metastases.