Modulation of lung-associated natural killer activity by resident and activated alveolar macrophages.
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).
Lemaire
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I
Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
St-Jean
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M
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003602:Cytotoxicity, Immunologic; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology*; D008274:Magnesium / Q000494:pharmacology; D017616:Magnesium Compounds; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012825:Silicon / Q000494:pharmacology; D017655:Silicon Compounds
D008070:Lipopolysaccharides; D017616:Magnesium Compounds; D017655:Silicon Compounds; D008274:Magnesium; C026325:attapulgite; D012825:Silicon