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

Intravenous (i.v.) administration of phagocytosable chitin particles (1 to 10 mu m) in C57BL/6 mice and SCID mice primed alveolar macrophages (M phi) within 3 days to field up to a 50-fold increase in their oxidative burst when elicited in vitro with phorbol myristate acetate (PMA). C57BL/6 mice pretreated dth monoclonal antibodies (MAbs) against mouse gamma interferon (IFN-gamma) or NK1.1 showed a markedly decreased level of alveolar M phi priming following injection of chitin particles. To confirm IFN-gamma production in vitro, spleen cells isolated from normal C57BL/6 mice and SCID mice were cultured with chitin particles. Significant IFN-gamma production was observed following stimulation with chitin but not with chitosan or latex bends, when spleen cells were treated with anti-NK1.1 MAb, IFN-gamma production was significantly inhibited. Another set of experiments showed that when C57BL/6 mice were pretreated i.v. with a small dose IFN-gamma, 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-gamma provided an up-regulation of IFN-gamma production by these phagocytosable particles. Taken together, the in vivo and in vitro results suggest that (i) the alveolar M phi priming mechanism is due, at least in part, to direct activation of M phi, by IFN-gamma, which is produced by NK1.1(+) CD4(-) cells; (ii) IFN-gamma would have an autocrine-like effect on M phi and make them more responsive to particle priming; and (nl) phagocytosis of particulates, probably by a postmembrane event such as interiorization, appears to be important for the up-regulation of alveolar M rho priming and IFN-gamma production.