We have discovered that gamma interferon appears to be the major macrophage-activating lymphokine in lectin supernatants and leads to a striking enhancement in the production of toxic oxygen intermediates (TOI) by human monocytes. Patients with severe lepromatous leprosy fail to make appreciable gamma-interferon and IL-2 in response to M. leprae. This is thought a factor in the extensive multiplication of the bacilli in dermal macrophages. Human dendritic cells (DC) are important accessory cells for the human allogeneic and syngeneic MLRs, for antibody formation versus T-cell-dependent antigens, and in the mouse as an important passenger leukocyte for graft recognition. Monoclonal antibodies prepared against mononuclear phagocytes have aided in the isolation of human DC. Progress was made in the isolation of the human low affinity Fc receptor and the C3bi receptor by means of monoclonal antibodies. Liganding of the Fc receptor initiates the secretion of TOI and arachidonate metabolites whereas the C3b receptor is inactive. Human monocytes, free of platelets, are important sources of thromboxane as well as leukotrienes B & C. Monocytes selectively bind to the surface of human endothelial cells (EC) triggering the release of prostacyclin (PEX) by EC. The monocyte product leukotriene C (LTC) also leads to PEX secretion. Endothelial cells also degrade LT-C via a gamma glutamyl transpeptidase. L. pneumophila is internalized via a unique coil-like structure and subsequently resides in a nonfused endosome. We have discovered that the Kupffer cell of the liver is selectively deficient in its ability to produce TOI, either in the presence or absence of gamma-IFN and is a permissive host for intracellular pathogens. The resistance of the liver is due to newly emigrated TOI producing monocytes, which localize in granulomas. (MB)
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