Abstract
Lipopolysaccharides (LPS) isolated from the outer membranes of gram negative bacteria have been demonstrated to modulate a spectrum of pathological and immunological events both in vitro and in vivo (14,15,23). Several lines of evidence have suggested that macrophages are not only stimulated by bacterial LPS (3,4,7,16) but may also be involved in the detoxification of this bacterial product (9,17,18). In recent studies designed to follow the fate of E. coli LPS after the uptake and catabolism of whole E. coli by macrophages, we demonstrated that LPS are exocytosed slowly from the macrophage. Furthermore, the LPS remaining within the macrophage at 72 hours, and the LPS released from the macrophage over that period, retain endotoxic activity (5,6). In this chapter, we provide evidence that the LPS remaining within the macrophage at 48–s72 hours is associated with macrophage phagocytic vacuoles, and that both the retained LPS and the exocytosed LPS have a significantly enhanced capacity to stimulate splenocytes. Parenthetically, our results also indicate that, as assessed by SDS-PAGE, macrophage processed LPS is enriched for higher molecular weight subunits relative to control LPS. Althrough the precise macrophages-induced biochemical altertions in LPS which contribute to enhances immunostimulatory activity remain to be elucidated, these data nevertheless provide evidence that macrophage processing of LPS may contribute to the local amplification of immunologicallly relevant events.
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References
P. M. Allen, D. I. Beller, J. Braun, and E. R. Unanue, The handling of Listeria monocytogenes by macrophages: the search for an immunologic molecule in antigen presentation, J. Immunol. 132: 323 (1984).
B. N. Ames and D. T. Dubin, The role of polyamines in the neutralization of pacteriophage deoxyribonucleic acid, J. Biol. Chem. 135: 769 (1960).
W. F. Doe and P. M. Henson, Macrophage stimulation by bacterial lipopolysaccharides. I. Cytolytic effect on tumor target cells, J. Exp. Med. 148: 544 (1978).
W. F. Doe, S. T. Yang, D. C. Morrison, S. J. Betz, and P. M. Henson, Macrophage stimulation by bacterial lipopolysaccharides. II. Evidence for differential signals delivered by lipid A and by protein rich fractions of LPS, J. Exp. Med. 148: 557 (1978).
R. L. Duncan, Jr., and D. C. Morrison, Fate of Escherichia coli lipopolysaccharide following the uptake of E. coli by murine macrophages in vitro, J. Immunol. 132: 1416 (1984).
R. L. Duncan, Activity of macrophage processed endotoxin, in: “Pathogenesis of Bacterial Infections,” G. G. Jackson and H. Thomas, eds., Proc. Grosse Ledder Symposium VIII, Springer-Verlag, Berlin (1985).
A. C. Eaves and W. R. Bruce, In vitro production of colony stimulating activity. I. Exposure of mouse peritoneal cells to endotoxins, Cell Tissue Kinet. 7:19 (1974).
A. G. Farr, M. E. Dorf, and E. R. Unanue, Secretion of mediators following T lymphocyte-macrophage interaction is regulated by the major histocompatibility complex, Proc. Natl. Acad. Sci. USA 74: 3542 (1977).
J. P. Filkins, Comparison of endotoxin detoxification by leukocytes and macrophages, Proc. Soc. Exp. Biol. Med. 137: 1396 (1971).
D. C. Morrison, Z. G. Oades, S. Vukajlovich, S. A. Goodman, and R. L. Duncan, Jr., Mechanism of action of endotoxin at the cellular level, in: “Mechanisms of Hepatocyte Injury and Death,” D. Keppler, H. Popper, L. Bianchi, and W. Reutter, eds., MTP Press, Lancaster (1983).
S. A. Goodman and D. C. Morrison, Selective association of lipid-rich R-like lipopolysaccharide (LPS) subunits with murine spleen cells, Mol. Imunol. 21: 689 (1984).
D. C. Morrison, R. L. Duncan, Jr., and S. A. Goodman, In vivo biological activities of endotoxin, in: “Bacterial Endotoxins: Structure, Biomedical Sugnificance and Detection wtih Limulus Amebocyte Lysate Test,” J. W. ten Cate, H. R. Buller, A. Struk, and J. Levin, eds., in press (1985).
D. C. Morrison, S. J. Betz, and D. M. Jacobs, Isolation of a lipid A bound polypeptide responsible for “LPS-initiated” mitogenesis of C3H/HeJ spleen cells, J. Exp. Med. 144: 840 (1976).
D. C. Morrison and J. L. Ryan, Bacterial endotoxins and host immune responses, Adv. Immunol. 28: 293 (1979).
D. C. Morrison and R. J. Ulevitch, The interaction of bacterial endotoxins with cellular and humoral mediation systems, Am. J. Pathol. 93: 527 (1978).
L. P. Ruco and M. S. Meltzer, Macrophage activation for tumor cytotoxic activity requires completion of a sequence of shortlived intermediary reactions, J. Immunol. 121: 2035 (1978).
S. H. Rutenburg, F. B. Schweinburg, and J. Fine, In vitro detoxification of bacterial endotoxin by macrophages, J. Exp. Med. 112:801 (1960).
R. A. Trejo and N. R. DiLuzio, Comparative evaluation of macrophage inactivation of endotoxin, Proc. Soc. Exp. Biol. Med. 144: 901 (1973).
E. R. Unanue, Antigen presenting function of the macrophage, Ann. Rev. Immunol. 2: 395 (1985).
E. R. Unanue, J. M. Kiely, and J. Calderon, The modulation of lymphocyte functions by molecules secreted by macrophages. II. Conditions leading to increased secretion, J. Exp. Med. 144: 155 (1976).
S. Vukajlovich and D. C. Morrison, Conversion of lipopolysaccharides to molecular aggregates with reduced subunit heterogeneity: demonstration of LPS responsiveness in “endotoxin-unresponsive” C3H/KeJ splenocytes, J. Immunol. 130: 2804 (1983).
S. W. Vukajlovich and D. C. Morrison, Lipid-A dependent lymphocyte proliferation in “endotoxin nonresponder” mice, Rev. Infect. Dis. 6: 528 (1984).
J. J. Wannemuehler, H. Kiyomo, J. L. Babb, M.S. Michalek, and J. R. McGhee, Lipopolysaccharide (LPS) regulation of the immune response: LPS converts germfree mice to sensitivity to oral tolerance induction, J. Immunol. 129: 959 (1982).
H. K. Ziegler and E. R. Unanue, Decrease in macrophage antigen catabolism by ammonia and chloraquin is associated with inhibition of antigen presentation to T cells, Proc. Natl. Acad. Sci. USA 79: 175 (1982).
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© 1986 Plenum Press, New York
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Duncan, R.L., Tesh, V., Morrison, D.C. (1986). Characterization and Localization of Lipopolysaccharides Following the Ingestion of E. Coli by Murine Macrophages in Vitro. In: Szentivanyi, A., Friedman, H., Nowotny, A. (eds) Immunobiology and Immunopharmacology of Bacterial Endotoxins. University of South Florida International Biomedical Symposia Series, vol 18. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2253-5_32
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DOI: https://doi.org/10.1007/978-1-4613-2253-5_32
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