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Terminal differentiation of human monocytic leukemia cells (THP-1 cells) was associated with the induction of c-fos, the down regulation of c-myb, and no significant change in the level of c-myc expression. Gamma interferon, which resulted in a slight decrease in c-myb but no change in c-fos or c-myc expression, had a transient antiproliferative effect without a morphological or functional differentiation of THP-1 cells. Resting human peripheral blood monocytes have a high c-fos, a low c-myc, and no detectable c-myb expression. These findings suggest that a switch in c-fos/c-myb expression is associated with the terminal differentiation of cells of the monocytic lineage.

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When mouse peritoneal cells in early phase-inflammatory exudates were cultured in vitro, the number of polymorphonuclear leukocytes (PMNs) rapidly decreased, whereas the number of macrophages gradually increased during culture. Macrophage growth was also induced by addition of effete PMNs or their debris to macrophage monolayers. This phenomenon was not restricted to senescent PMNs, because effete spleen cells or effete tumor cells also induced macrophage growth. The activity of these cell debris was stable on heating at 100 degrees C and was partially recovered in the lipid fraction. These data suggest that tissue macrophages may proliferate when they scavenge effete PMNs or other host cells and that these cell debris may be important mediators in inducing growth of peripheral macrophages in inflammation and tumors or the normal steady state.

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The biological characteristics of mouse macrophage-like cell line (MMC-1) are described. This cell line has been cultured in vitro for more than 20 months. MMC-1 cells are adherent to typical morphology of macrophages, but bigger in size than those of the uncultivated. They are actively phagocytic with abundant Fc receptors. The karyotypes are mostly pantaploidy. This cell line provides a useful tool for the biological and immunological study of macrophage.

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Liver tissue from rats of different age has been cultured. The samples were obtained by surgical biopsy. A relationship between the obtained growth in culture and the animal age was established. A relationship between the obtained growth in culture and the animal age was established. The liver from young and weanling rats grows larger and earlier than the adult liver. The cells obtained in culture have been classified in five different types according to morphological criteria.

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Pure cultures of chicken macrophages were characterized functionally and transformed by avian myeloblastosis virus. Transformed cells exhibited an altered function. The efficiency of transformation was limited by the mitotic activity of the macrophages.

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Thirteen human T cell leukemia-lymphoma cell lines were examined to determine whether or not they released a product into the media in which they were growing which could stimulate granulocyte-macrophage colony formation by human hemopoietic cells. None of the cell lines studied released colony stimulating activity.

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A modified sieving technique has been developed to isolate pure glomeruli from monkey, sheep, dog, rabbit and rat kidney. Glomeruli from all these species have been grown in tissue culture and the glomerular cell outgrowth studied by light microscopy and time-lapse cinemicroscopy. The pattern of growth was the same for all the species studied. In all species, three cell populations have been identified with the features of epithelial cells, mesangial cells and macrophages, although the latter population is only rarely observed. The morphology and culture characteristics of each cell type in all species were similar, including the relative numbers present and rates of division.

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Glucan, a potent reticuloendothelial stimulant, is a glucopyranose polysaccharide derived from zymosan. Because of glucan's potential as an immunotherapeutic agent, we performed studies in order to determine its effect on granulopoiesis and macrophage production in mice. One week after the i.p. injection of 4 mg of glucan, there was a tenfold increase in colony-forming cells in the spleen and approximately a twofold increment of cells in the bone marrow and the peritoneal cavity capable of colony formation in vitro. There was a relative and absolute increase in the number of pure macrophage colonies from bone marrow and spleen. The total macrophage content in spleen, peritoneal cavity, and bone marrow as also increased in the treated mice. Serum from glucan-injected mice had high colony-stimulating activity levels, and the peritoneal macrophages elaborated increased colony-stimulating activity in vitro as compared to controls. Peripheral white blood cell counts were two times greater than those of control in the glucan-treated mice. These studies indicate that glucan administration results in increased granulocyte and macrophage production. The enhanced leukopoiesis is probably mediated in part by augmented release of colony-stimulating activity from macrophages. These observations suggest that the use of glucan as an immunotherapeutic agent can result in an increased number of available effector cells.

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Granulocytic extracts (GE) of different sources, presumably containing the granulocytic chalone, were prepared in different laboratories and purified to some extent. They specifically inhibited the formation of granulocyte and macrophage colonies in agar. The effect was however most pronounced on granulocyte and mixed granulocyte-macrophage colonies, and less on macrophage types. Addition of GE to bone marrow cells at the time of plating in agar, as well as short incubation of the cells together with GE prior to plating, inhibited subsequent colony formation. The inhibitory effect could easily be reversed by washing the cells with an excess of medium prior to plating during the first hour of preincubation, but not after five hours. Increasing the doses of colony stimulating activity (CSA) (at low doses of GE) released the inhibitory effect, but not at high doses of GE. The inhibitory effect of GE on colony formation was dose dependent down to almost 100% inhibition. No apparent cytotoxic effect of GE on bone marrow cells could be found and lymphoblastic cells were not inhibited. Extracts containing a specific inhibitor of erythropoiesis (EIF) stimulated myelopoietic colony formation in agar.

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Pulmonary alveolar macrophages were obtained from healthy volunteers by saline pulmonary lavage, and aryl hydrocarbon hydroxylase was measured in the cells. Enzyme activity was low in cells from five nonsmokers with a mean of 0.008+/-0.004 U/10(6) cells. Cells obtained from nine cigarette smokers contained higher enzyme levels, with a mean of 0.095+/-0.024 U/10(6) cells. A former cigarette smoker was lavaged on five occasions. Enzyme activity during two lavages 4 mo apart were 0.010 and 0.009 U/10(6) cells, respectively. 1 wk after smoking was resumed, the enzyme activity rose slightly to 0.013, and reached 0.041 U/10(6) cells by 1 mo. Upon cessation of smoking, the enzyme activity returned to control levels by the next lavage, 2 mo later. These data indicate that aryl hydrocarbon hydroxylase may be induced in pulmonary alveolar macrophages of subjects chronically exposed to cigarette smoke.

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Carrageenan, a sulfated polygalactose which suppresses established delayed hypersensitivity in vivo, is shown to be cytotoxic to macrophages but not to lymphocytes in vitro. This cytotoxicity depends on the carrageenan concentration and degree of lysosomal differentiation but is independent of serum. Survival of macrophages in the presence of carrageenan can be enhanced temporarily by corticosteroids. Ultrastructural studies reveal that carrageenan is readily taken up by macrophages and stored in lysosomes, which subsequently swell and rupture, apparently resulting in cell death. The presence of corticosteroids temporarily retards lysosome swelling. It is suggested that carrageenan may exert its cytotoxic effect by causing osmotic rupture of lysosomes. The possible immunologic significance of these findings is discussed.

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