DIFFERENTIAL MODULATION OF THE EFFECTS OF LIPOPOLYSACCHARIDE ON MACROPHAGES BY A MAJOR OUTER-MEMBRANE PROTEIN OF PROTEUS-MIRABILIS

We previously showed that a major protein isolated from purified cell walls of Proteus mirabilis (39-kDa protein) is a strong modulator of t he specific immune responses to LPS from this bacterium in mice. When mixed with LPS before immunization, this protein enhances T cell-depen dent, IgG antibody-producing cell responses specific for LPS. Furtherm ore, complexes of the 39-kDa protein with LPS drastically inhibit the production of oxygen radicals by murine macrophages activated with LPS , as measured in a chemiluminescence assay. In the present report, we have further investigated possible modulating effects of the protein a t the level of LPS-macrophage interaction. When mixed with LPS, the 39 -kDa protein inhibited IL-1 production by murine macrophages derived f rom bone marrow in a dose-dependent manner, as determined in an IL-2-d ependent IL-1 assay. On the other hand, the protein had little effect on LPS-mediated suppression of MHC class II expression on the surface of macrophages induced with IFN-gamma. Some abrogation of suppression was observed, but the amounts of protein needed for this effect were q uite large, in comparison with the amounts rendering inhibition of IL- 1 production. In contrast, the 39-kDa protein enhanced the LPS-induced cytotoxicity of macrophages against L929 target cells, primarily as t he result of production of TNF. These results show that the 39-kDa pro tein is a potent modulator of the interaction of LPS with macrophages, exerting its effects in a differential manner with respect to various parameters of LPS-induced activation of macrophages.