MACROPHAGE PERMISSIVENESS FOR LEGIONELLA-PNEUMOPHILA GROWTH MODULATEDBY IRON

We have investigated the modulation of iron in two populations of macr ophages which differ in susceptibility to Legionella pneumophila intra cellular proliferation. Previously, we reported that thioglycolate eli cited peritoneal macrophages obtained from the inbred A/J mouse strain readily support the intracellular growth of L. pneumophila, while res ident macrophages from the same strain do not. In this study, we show that A/J elicited macrophages exhibit markedly higher expression of tr ansferrin receptor and intracellular iron content than A/J resident ma crophages. Furthermore, apotransferrin and desferrioxamine inhibited t he intracellular proliferation of L. pneumophila in elicited macrophag es, and this suppression was reversed by the additions of Fe-transferr in or ferric nitrilotriacetate. Fe-transferrin and ferric nitrilotriac etate did not further increase the intracellular proliferation oft. pn eumophila in thioglycolate-elicited macrophages. However, ferric citra te and ferric nitrilotriacetate stimulated in a dose-dependent manner the growth of L. pneumophila in resident macrophages. Furthermore, equ imolar concentrations of desferrioxamine reversed the stimulatory effe ct of iron in these resident cells. These data provide evidence suppor ting the hypothesis that differences in susceptibility to L. pneumophi la growth between permissive elicited macrophages and nonpermissive re sident macrophages from the A/J mouse strain are due to intracellular availability of iron.