The Development of Macrophages from Large Mononuclear Cells in the Blood of Patients with Inflammatory Disease

Abstract

The origin and function of the increased of “atypical lymphocytes” which appear in the blood of patients with many inflammatory diseases is not known. Leukocyte suspensions from eight patients with systemic lupus erythematosus (SLE), five patients with other rheumatic diseases, and five patients with infectious diseases were pulse-labeled with tritiated thymidine (Tdr-³H) and sampled after 5 and 72 hr in vitro. Radioautographs indicated that 35% of the total large, nonphagocytic mononuclear leukocytes incorporated Tdr-³H during the initial 5 hr of culture. Tdr-³H-labeled large phagocytic or glass-adherent cells were observed only infrequently. After 72 hr one-third of the original number of Tdr-³H-labeled cells from patients with SLE developed the morphology of macrophages and the capacity to phagocytose latex particles. Similar findings were observed in patients with other rheumatic diseases and bacterial infections. In contrast, the thymidine-labeled cells from patients with infectious hepatitis and infectious mononucleosis were poorly viable in culture and rarely became macrophages. Tdr-³H-labeled small lymphocytes were uncommon. The present experiments suggest that in patients with certain inflammatory diseases large, proliferating “lymphocytelike” cells are very immature monocyte precursors which appear in response to tissue injury. These DNA-synthesizing cells together with mature monocytes may serve as the circulating source of macrophages.