Alveolar macrophage suppression of canine bronchoalveolar lymphocytes: the role of prostaglandin E2 in the inhibition of mitogen-responses.

Unfractionated bronchoalveolar cells (BAC), obtained by pulmonary lavage, are composed of alveolar macrophages (65%) and bronchoalveolar lymphocytes (29%). We examined interactions between normal canine alveolar macrophages and bronchoalveolar lymphocytes to determine whether these macrophages suppress mitogen responses of lymphocytes by secretion of prostaglandins. Mitogen responses of unfractionated BAC were enhanced by culture in the presence of indomethacin or by depleting adherent cells from BAC by nylon wool adsorption (column-purified BAC). Addition of indomethacin to column-purified BAC failed to further enhance mitogen responses. Radioimmunoassay of PGE2 in the supernatants of cell-cultures demonstrated that adherent cells (95% alveolar macrophages) accounted for the majority of PGE2 produced by unfractionated BAC; column-purified BAC produced only low levels of PGE2. Addition of exogenous PGE2 to cultures of either unfractionated BAC or column-purified BAC resulted in suppression of mitogen responses of both preparations of cells at concentrations of PGE2 elaborated by alveolar macrophages in vitro. Co-culture of plastic-adherent, irradiated alveolar macrophages with purified bronchoalveolar lymphocytes resulted in suppression of mitogen responses of lymphocytes to levels observed in naturally occurring populations of BAC. Taken together, these data indicate that normal canine alveolar macrophages present in populations of unfractionated BAC suppress proliferative responses of bronchoalveolar lymphocytes through elaboration and release of indomethacin-inhibitable materials that include PGE2. In additional studies, co-culture of alveolar macrophages with purified bronchoalveolar lymphocytes in the presence of indomethacin not only blocked the sup pressive activity of alveolar macrophages, but actually resulted in enhancement of mitogen responses of bronchoalveolar lymphocytes. The latter data suggest that alveolar macrophages exert both suppressing and enhancing influences on bronchoalveolar lymphocytes and that it is the net effect that determines in which direction lymphocyte function is altered.