Abstract
A murine leukemia x LM fibroblast hybrid cell line with immune augmenting properties stimulated resistance toMycobacterium avium complex (MAC) in mouse peritoneal macrophages, and in immune deficient beige mice (C57BL/6/bgj/bgj). The proliferation of MAC in mouse peritoneal macrophages was inhibited by medium conditioned by the growth of the hybrid cells (hybrid cell-CM). Under similar circumstances, media conditioned by the growth of LM cells (LM cell-CM), a mouse fibroblast cell line used as one parent in forming the hybrid cell, was exhibited no inhibitory effect. Treatment of mouse peritoneal macrophages with hybrid cell-CM, but not with LM cell-CM, stimulated the expression of each of four previously described macrophage activation antigens, suggesting that the hybrid cells, formed immunomodulators in addition to those formed by LM cells. Furthermore, the morphology of the macrophages following treatment with hybrid cell-CM was clearly distinguishable from that following exposure of the cells to LM cell-CM. The therapeutic effects of hybrid cells on the progression of MAC-infection were indicated by the prolonged survival of MAC-infected immune-deficient beige mice. One hundred percent of treated animals survived more than 60 days, while untreated animals died in approximately 22 days.
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References Cited
Adams, D. O. and Hamilton, T. A., The cell biology of macrophage activation.Ann. Rev. Immunol., 2, 283–318 (1984).
Appelberg, R., Protective role of interferon gamma, tumor necrosis factor alpha and interleukin-6 inMycobacterium tuberculosis andMycobacterium avium infections.Immunobiol., 191, 520–525 (1994).
Baker, P. E., Gillis, S. and Smith, K. A., Monoclonal cytolytic T-cell lines.J. Exp. Med., 149, 273–278 (1979).
Baron, E. J. and Young, L. S., Amikacin, ethambutol and rifampin for treatment of disseminatedMycobacterium avium-intracellulare infections in patients with acquired immunodeficiency syndrome.Diagn. Microbiol. Infect. Dis., 5, 215–220 (1986).
Bermudez, L. E. and L. S. Young., Tumor necrosis factor, alone or in combination with IL-2, but not IFN-γ, is associated with macrophage killing ofMycobacterium avium complex.J. Immunol.,140 3006–3013 (1988).
Bermudez, L. E. and L. S Young., Recombinant granulocyte-macrophage colony stimulating factor activates human macrophages to inhibit or killMycobacterium avium complex.J. Leuk. Biol., 48, 67–73 (1990).
Bermudez, L. E., Wu, M. and Young, L. S., Interleukin-12-stimulated natural killer cells can activate human macrophages to inhibit growth ofMycobacterium avium Infect. Immun., 63, 4099–4104 (1995).
Bertram, M. A., Interlied, C. B., Yadegar, S., Kolanoski, P., Yamada, J.K. and Young, L. S., Confirmation of the beige mouse model for study of disseminated infection withMycobacterium avium complex.J. Infect. Dis., 154, 194–195 (1986).
Chow, H. S., Hagen, K., Kaizer, H. and Cohen, E. P., Formation of macrophage colony-stimulating factor by murine leukemia x fibroblast hybrid cells.J. Biol. Resp. Mod., 6, 446–456 (1987).
Cohen, E. P. and Hagen, K., Leukemia x fibroblast hybrid cells augment the antibody response to sheep red blood cells on inbred mice.Immunol., 56, 615–623 (1985).
Douvas, G. S., Looker, D. L., Vatter, A. E., and Crowle, A. J., Interferon-γ activates human macrophages to become tumoricidal and leishmanicidal but enhances replication of macrophage-associated mycobacteria.Infect. Immun., 50, 1–8 (1985).
Garber, S. L., Chang, I. and Cohen, E. P., Persistence of the immunoprotective effects of leukemia and fibroblast hybrid cells toward leukemia in histocompatible mice.Leuk. Res., 8, 255–266 (1984).
Hartley, J. W., Fredrickson, T. N., Yetter, R. A., Makino, M. and Morse, H. C., Retrovirus-induced murine acquired immunodeficiency syndrome: natural history of infection and differing susceptibility of inbred mouse strainsJ. Virol., 63, 1223–1231 (1989).
Hsu, N., Young, L. S. and Bermudez, L. E., Response to stimulation with recombinant cytokines and synthesis of cytokines by murine intestinal macrophages infected with theMycobacterium avium complex.Infect. Immun., 63, 528–533 (1995).
Hu-Li, J., Ohara, J., Watson, C., Tsang W. and Paul, W. E., Derivation of a T cell line that is highly responsive to IL-4 and IL-2 (CT. 4R) and of an IL-2 hyporesponsive mutant of that line (CT.4S).J. Immunol., 142, 800–807 (1989).
Ihle, J. N., Keller, J., Greenberger, J. S., Henderson, L. and Yetter, R. A., Phenotypic characterization of cell lines required for IL-3 growth.J. Immunol., 129, 1377–1383 (1982).
Kim, B. S., Liang, W. and Cohen, E. P., Tumor specific immunity induced by somatic hybrids. I. Lack of relationship between immunogenicity and tumorgenicity of selected hybrids.J. Immunol., 123, 733–738 (1979).
Lee, J. C., Badger, A. M. and Johnson, W. J., Human non-interferon macrophage-activating factor: biological and biochemical characterization.Adv. Exp. Med. Biol., 239, 217–221 (1988).
Nakawara, A. and Nathan, C. F., A simple method for counting adherent cells: application to cultured human monocytes, macrophages and multinucleated giant cells.J. Immunol. Methods, 56, 261–268 (1983).
Orincote, S. F. and Dinarello, C. A., Characterization of a subclone (D10S) of the D10.G41 helper T cell clone which proliferates to submolar concentrations of interleukin-1 in the absence of mitogensCytokine, 1, 14–19 (1989).
Paulnock, D. M. and Lambert, L. E., Identification and characterization of monoclonal antibodies specific for macrophages at intermediate stages in the tumoricidal activation pathway.J. Immunol., 144, 765–773 (1990).
Pierce, M., Crampton, S., Henry, D., Heifets, L., LaMarca, A., Montecalvo, M., Wormser, G. P., Jablonowski, H., Jemsek, J., Cynamon, M., Yangco, B. G., Notario, G. and Craft, J. C., A randomized trial of clarithromycin as prophylaxis against disseminatedMycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome.New. Engl. J. Med., 335, 384–391 (1996).
Reynolds, D. S., Boom, W. H. and Abbas, A. K., Inhibition of B lymphocyte activation by interferon-γ.J. Immunol., 139, 767–773 (1987).
Saunders, B. M., Zhan, Y. and Cheers, C., Endogenous interleukin-12 is involved in resistance of mice toMycobacterium avium complex infection.Infect. Immun., 63, 4011–4015 (1995).
Weiss, M. C. and Chaplain, M., Expression of differentiated functions in hepatoma cell hybrids: Reappearance of tyrosine aminotransferase inducibility after loss of chromosomes.Proc. Natl. Acad. Sci. USA, 68, 3026–3030 (1975).
Yang, J. Y., Schwartz, A. and Henderson, E. E., Inhibition of 3′ azido-3′ deoxythymidine-resistant HIV-1 infection by dehydroepiandrosteronein vitro.Biochem. Biophys. Res. Commun., 201, 1424–1432 (1994).
Young, L. S., Inderlied, C. B., Berlin, O. G. and Gottlieb, M. S., Mycobacterial infections in AIDS patients, with an emphasis on theMycobacterium avium complex.Rev. Infect. Dis., 8, 1024–1033 (1986).
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Kim, T.S., Cohen, E.P. Macrophage-activating factors produced by murine leukemia x fibroblast hybrid cells stimulates resistance toMycobacterium avium complex. Arch. Pharm. Res. 20, 225–233 (1997). https://doi.org/10.1007/BF02976149
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DOI: https://doi.org/10.1007/BF02976149