Spectrum of immunoregulatory functions and properties of human alveolar macrophages

In health, pulmonary alveoli are maintained free of inflammatory responses to inhaled foreign antigens. The specific role of alveolar macrophages (AM) in modulating the local cellular immune response to antigens is controversial. Immunoregulatory function and properties of AM and blood monocytes (MN) were compared. The AM were obtained by bronchoalveolar lavage of healthy volunteers, MN by adherence of peripheral blood mononuclear cells to plastic. These accessory cells were added in increasing ratios to a responder population rendered rigorously accessory cell-dependent by nylon wool adherence and depletion of cells bearing the surface Class II MHC determinant, HLA-DR. At low ratios of mononuclear phagocytes to lymphocytes (≤ 1:10), MN and AM supported significant and comparable blastogenic responses to tetanus toxoid (³H-thymidine incorporation at a 1:10 ratio was 9,697 ± 2,508 for MN and 8,969 ± 1,454 for AM, mean cpm ± SE, n = 9, p = NS) and other antigens. Interleukin-1 (IL-1) activity in supernatants of MN stimulated with lipopolysaccharide (LPS), 10 μg/ml, was 115 ± 28 versus 67 ± 21 U/ml in supernatants of AM (n = 9, p > 0.2). At suboptimal concentrations of LPS, however, MN expressed more IL-1 activity than did AM. The specific mean fluorescence intensity of surface expression of HLA-DR determinants as assessed by flow cytometry was similar for MN and AM. At the higher ratio of 1:2, MN supported 32% increased responses to tetanus toxoid compared with that at 1:5 (p <0.05). In contrast, AM at a ratio of 1:2 suppressed lymphocyte response by 69% (p <0.001). Suppression by AM was partially reversed by indomethacin. Suppressive activity of AM from smokers for responses of nylon wool nonadherent cells to antigen was greater than in nonsmokers (n = 4, p <0.05) and was also partially reversed by indomethacin. These studies show that AM are fully capable of accessory activity at low ratios; yet, at high ratios of AM to lymphocytes in vitro, suppression by AM predominates. These observations demonstrate that human AM might either enhance immune function or exert an antiphlogistic effect within the alveolar milieu in response to inhaled foreign antigens.