Interleukin-3 (IL-3) stimulates the clonal growth of pulmonary alveolar macrophage of the mouse: role of IL-3 in the regulation of macrophage production outside the bone marrow

Interleukin-3 (IL-3) is one of the hematopoietic growth factors that regulates the growth and differentiation of pluripotent stem cells, thereby leading to the production of all the major blood cell types. The role of IL-3 in the regulation of pulmonary alveolar macrophage (PAM) production was investigated. IL-3 stimulated the proliferation and clonal growth of murine PAM with a dose-response curve similar to that of bone marrow granulocyte-macrophage colony-forming cells. The IL- 3-induced colony formation by cells outside the bone marrow appeared to be unique to PAM; IL-3 failed to cause colony formation by both peritoneal exudate macrophages (PEM) and blood monocytes. Unlike bone marrow stem cells, PAM are unipotential and in vitro gave rise to only mononuclear phagocytes under the influence of IL-3. Nevertheless, cells derived from PAM cultures in media containing IL-3 displayed a high degree of heterogeneity in terms of their Fc receptor-mediated phagocytic activity. At low concentrations, IL-3 induced a synergistic response with colony-stimulating factor 1 (CSF-1), which resulted in an enhanced proliferative capacity of PAM. A synergistic effect was also observed by short-term exposure of PAM to IL-3 followed by incubating with CSF-1 alone. This study shows that IL-3 exhibited a macrophage growth factor activity unique to PAM.