Modulation of Lung-Associated Natural Killer Activity by Resident and Activated Alveolar Macrophages

Abstract

Alveolar macrophages (AM) freshly obtained by bronchoalveolar lavage suppressed significantly, in a dose-dependent fashion, lung interstitial lymphocytes cytotoxicity against the NK-sensitive target cells, YAC-1. Kinetic experiments revealed that AM-mediated suppression of NK activity was seen following short-term incubation of AM with lymphocytes (4 h) and was unchanged after a 24 h co-culture period. Freshly obtained lung lymphocytes and lymphocytes incubated for 24 h were similarly inhibited by AM. In addition, incubation of AM for 24 h did not abrogate their suppressive effect on lung NK activity. Interestingly, AM-conditioned media, also caused a significant inhibition of lung NK activity. Furthermore, in vitro activation of AM with lipopolysaccharide (LPS, 5 micrograms/ml) and muramyl dipeptide (MDP, 20 micrograms/ml) significantly enhanced the inhibitory effect of AM on lung NK activity. Similarly, in vivo activation of AM locally by intratracheal instillation of attapulgite, an inflammatory agent, resulted in greater AM-mediated down regulation. Taken together, these data indicate that lung NK activity is modulated by locally derived factors and suggest that pharmacologic manipulation of AM may play a determining role in the activation of lung NK activity by biological response modifiers (BRM).