Alveolar macrophage priming by intravenous administration of chitin particles, polymers of N-acetyl-D-glucosamine, in mice

Abstract

Intravenous (i.v.) administration of phagocytosable chitin particles (1 to 10 mm) in C57BL/6 mice and SCID mice primed alveolar macrophages (Mf) within 3 days to yield up to a 50-fold increase in their oxidative burst when elicited in vitro with phorbol myristate acetate (PMA). C57BL/6 mice pretreated with monoclonal antibodies (MAbs) against mouse gamma interferon (IFN-g) or NK1.1 showed a markedly decreased level of alveolar Mf priming following injection of chitin particles. To confirm IFN-g production in vitro, spleen cells isolated from normal C57BL/6 mice and SCID mice were cultured with chitin particles. Significant IFN-g production was observed following stimulation with chitin but not with chitosan or latex beads. When spleen cells were treated with anti-NK1.1 MAb, IFN-g production was significantly inhibited. Another set of experiments showed that when C57BL/6 mice were pretreated i.v. with a small dose IFN-g, a higher level of priming was induced with not only phagocytosable chitin particles but also phagocytosable chitosan and even latex beads. Likewise, the spleen cell cultures preconditioned with IFN-g provided an up-regulation of IFN-g production by these phagocytosable particles. Taken together, the in vivo and in vitro results suggest that (i) the alveolar Mf priming mechanism is due, at least in part, to direct activation of Mf by IFN-g, which is produced by NK1.11 CD42 cells; (ii) IFN-g would have an autocrine-like effect on Mf and make them more responsive to particle priming; and (iii) phagocytosis of particulates, probably by a postmembrane event such as interiorization, appears to be important for the up-regulation of alveolar Mf priming and IFN-g production. Originally published Infection and Immunity, Vol. 65, No. 5, May 1997