Inhibition of lymphokine-activated killer cell function by human alveolar macrophages.
Tissue- and organ-specific factors may be important in the regulation of cytotoxic lymphocytes. We therefore examined the ability of human alveolar macrophages (AMs) to alter the tumoricidal function of lymphokine-activated killer cells (LAK cells). AMs, obtained by bronchoalveolar lavage from healthy volunteers, or peripheral blood monocytes were added to a standard 4-h chromium release LAK assay at varying concentrations. AMs severely inhibited the killing of both NK-sensitive (K562) and NK-resistant (M14) tumor cells [42 +/- 2.6% (SEM) inhibition of M14 killing at the 0.125:1 AM:LAK ratio and 83 +/- 2.3% inhibition at the 1:1 ratio, n = 9]. Peripheral blood monocytes, in contrast, were only one-eighth as inhibitory as AMs. A positive smoking history was associated with a 3- to 7-fold increase in the number of AMs recovered by bronchoalveolar lavage but had no effect on the inhibition produced per AM cell. The mechanism of inhibition was investigated. Formalin fixation produced an 8-fold reduction in the inhibitory capacity of AMs, suggesting the need for active metabolism or an intact cell membrane. No soluble mediator could be detected with a two-chamber Transwell system, in 24-h AM culture supernatants, or following blocking experiments with indomethacin, catalase, or superoxide dismutase. Binding studies demonstrated selective binding between LAK cells and AMs, yet AMs were not susceptible to LAK-mediated lysis under the usual assay conditions. In summary, AMs are potent inhibitors of in vitro LAK function. Inhibition requires direct cell contact and is independent of soluble reactive oxygen species, prostaglandins, or activation by tobacco smoking. Inhibition is not due to lysis of the AM as a competitive cold target. These results suggest that AMs may actively limit antitumor cytotoxic responses in the lung.
Roth
M D
MD
Division of Pulmonary Medicine, UCLA School of Medicine 90024.
Golub
S H
SH
D002450:Cell Communication; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D007962:Leukocytes / Q000502:physiology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000276:immunology*; D012907:Smoking / Q000276:immunology; D014407:Tumor Cells, Cultured
D007376:Interleukin-2