Murine alveolar macrophage-mediated lymphocyte cytostasis: kinetics and mechanisms

Abstract

Recent reports have demonstrated that alveolar macrophages (AM) from several species regulate antigen- and mitogen-induced blastogenesis. In this study, we confirm that murine AM also mediate lymphocyte cytostasis and define, in part, the mechanism involved. AM were found to inhibit homologous splenocyte responses to concanavalin A in a dose-dependent manner. The inclusion of 1 AM:10 lymphocytes abrogated mitogenesis. Kinetic studies revealed that maximal inhibition of the splenocyte response required the inclusion of AM at culture initiation, stimulation of splenocytes with an optimal Con A dose, and an optimal incubation period of 72 hr. In addition, suppression of Con A-induced blastogenesis by AM was not genetically restricted, as Balb/c AM suppressed allogeneic CBA/J spleen cells comparably to homologous control cells. The addition of either catalase or indomethacin to partially suppressed cultures (containing 3% AM) totally reversed the inhibition. In contrast, catalase did not protect lymphocytes from absolute suppression mediated by higher AM numbers (10% AM), while indomethacin offered partial protection. A synergistic effect was noted upon the addition of both substances. Thus, prostaglandin and hydrogen peroxide released by AM contribute to the suppressive effects of these cells. © 1982