Heterogeneity of immunologic function among subfractions of normal rat alveolar macrophages

Rat alveolar macrophages were examined for the presence of subpopulations with different capacities for modulation of mitogen-induced lymphocyte proliferation and production of the monokine, Interleukin-1 (IL-1). Alveolar macrophages lavaged from normal rats were separated into 5 density fractions by centrifugation through a continuous gradient of isosmotic colloidal silica (Percoll). Measurement of cell size and endogenous peroxidase suggested that the cells fractionated by density represented alveolar macrophages at different levels of cell maturation. Alveolar macrophages from each of the density fractions were cultured with whole lymph node cells and the mitogens, concanavalin-A and phytohemagglutinin. Functional heterogeneity was demonstrated among the fractionated cells with respect to suppression of lymphocyte mitogenesis. Alveolar macrophages from intermediate density fractions suppressed mitogenesis in a dose-dependent manner, whereas alveolar macrophages from both the lowest and the highest density fractions had minimal effect on lymphocyte proliferation. When adherence-depleted lymph node cells were used in the mitogenesis assay, rat alveolar macrophages functioned poorly in support of lymphocyte proliferation, and no uniquely supportive alveolar macrophage subfractions were identified. Functional heterogeneity was also demonstrated for production of IL-1. Maximal IL-1 production was associated with the most dense alveolar macrophages, with progressively less IL-1 produced by lower density alveolar macrophage subfractions. The results confirm functional subpopulations of rat alveolar macrophages with respect to the suppression of lymphocyte mitogenesis and the production of Interleukin-1. Such functional subpopulations of alveolar macrophages may reflect the presence of cells at varying levels of cell maturation.