Activation of rat alveolar macrophages and protection against i.v. injected tumor cells by intratracheal administration of trehalose dimycolate

Abstract

Intratracheal (i.t.) administration of trehalose dimycolate (TDM) in saline as liposomes induces a transient inflammatory effect. Limited granulomas appeared in some peribronchial areas but most subsided after a few weeks. The alveolar macrophages were activated as judged by their cytostatic activity against the syngeneic P77 fibrohistiocytoma 3 days after administration of 0.2 mg TDM. The NK activity of the lymphocytes of the lung microcirculation did not increase and diminished slightly between 1 and 3 days after TDM administration, thus suggesting that macrophages might be the main effector cells responding to TDM. Repeated i.t. TDM administration protected rats against the development of colonies in the lung after i.v. injection of 5 X 10(5) P77 cells. The survival of the rats was significantly increased. Thus, in this system, a relationship exists between activation of alveolar macrophages and protection against colonies arising from i.v. injected tumor cells.