Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Jan;82(2):282–286. doi: 10.1073/pnas.82.2.282

Macrophage activation by monosaccharide precursors of Escherichia coli lipid A.

M Nishijima, F Amano, Y Akamatsu, K Akagawa, T Tokunaga, C R Raetz
PMCID: PMC397021  PMID: 3881760

Abstract

Certain Escherichia coli mutants defective in phosphatidylglycerol biosynthesis accumulate two novel glycolipids, designated X and Y. Lipid X is a diacylglucosamine 1-phosphate bearing beta-hydroxymyristoyl groups at positions 2 and 3, and lipid Y has the same structure as X, except for the additional presence of a palmitoyl moiety on the N-linked beta-hydroxymyristate. We have examined the activities of X, Y, and several related compounds as activators of macrophages. Both X and Y induce morphological changes (spreading), prostaglandin E2 synthesis, and killing of tumor cells by mouse peritoneal macrophages in vitro, properties with which lipopolysaccharide and lipid A are also endowed. Both glycolipids have similar effects on the macrophage-like mouse cell line J774.1. Selective removal from lipid X of either the ester-linked beta-hydroxymyristate at position 3 or the phosphate at position 1 abolishes activity. Our results show that the monosaccharides X and Y retain some of the properties of intact lipopolysaccharide and lipid A with respect to macrophage activation. Because the structures of X and Y are defined, our findings should facilitate the elucidation of the molecular mechanism of macrophage activation by lipid A.

Full text

PDF
282

Images in this article

283Image
on p.283
283Image
on p.283
283Image
on p.283
283Image
on p.283
283Image
on p.283

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akagawa K. S., Tokunaga T. Appearance of a cell surface antigen associated with the activation of peritoneal macrophages in mice. Microbiol Immunol. 1982;26(9):831–842. doi: 10.1111/j.1348-0421.1982.tb00229.x. [DOI] [PubMed] [Google Scholar]
  2. Alexander P., Evans R. Endotoxin and double stranded RNA render macrophages cytotoxic. Nat New Biol. 1971 Jul 21;232(29):76–78. doi: 10.1038/newbio232076a0. [DOI] [PubMed] [Google Scholar]
  3. Blanden R. V. Modification of macrophage function. J Reticuloendothel Soc. 1968 Jun;5(3):179–202. [PubMed] [Google Scholar]
  4. Bulawa C. E., Raetz C. R. The biosynthesis of gram-negative endotoxin. Identification and function of UDP-2,3-diacylglucosamine in Escherichia coli. J Biol Chem. 1984 Apr 25;259(8):4846–4851. [PubMed] [Google Scholar]
  5. Chedid L., Parant M., Damais C., Parant F., Juy D., Galelli A. Failure of endotoxin to increase nonspecific resistance to infection of lipopolysaccharide low-responder mice. Infect Immun. 1976 Mar;13(3):722–727. doi: 10.1128/iai.13.3.722-727.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohn Z. A. Activation of mononuclear phagocytes: fact, fancy, and future. J Immunol. 1978 Sep;121(3):813–816. [PubMed] [Google Scholar]
  7. Fidler I. J., Darnell J. H., Budmen M. B. Tumoricidal properties of mouse macrophages activated with mediators from rat lymphocytes stimulated with concanavalin A. Cancer Res. 1976 Oct;36(10):3608–3615. [PubMed] [Google Scholar]
  8. Galanos C., Freudenberg M. A., Lüderitz O., Rietschel E. T., Westphal O. Chemical, physicochemical and biological properties of bacterial lipopolysaccharides. Prog Clin Biol Res. 1979;29:321–332. [PubMed] [Google Scholar]
  9. Galanos C., Rietschel E. T., Lüderitz O., Westphal O. Interaction of lipopolysaccharides and lipid A with complement. Eur J Biochem. 1971 Mar 1;19(1):143–152. doi: 10.1111/j.1432-1033.1971.tb01298.x. [DOI] [PubMed] [Google Scholar]
  10. Karnovsky M. L., Lazdins J. K. Biochemical criteria for activated macrophages. J Immunol. 1978 Sep;121(3):809–813. [PubMed] [Google Scholar]
  11. Kotani S., Takada H., Tsujimoto M., Ogawa T., Harada K., Mori Y., Kawasaki A., Tanaka A., Nagao S., Tanaka S. Immunobiologically active lipid A analogs synthesized according to a revised structural model of natural lipid A. Infect Immun. 1984 Jul;45(1):293–296. doi: 10.1128/iai.45.1.293-296.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. MACKANESS G. B. THE IMMUNOLOGICAL BASIS OF ACQUIRED CELLULAR RESISTANCE. J Exp Med. 1964 Jul 1;120:105–120. doi: 10.1084/jem.120.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Matsuura M., Kojima Y., Homma J. Y., Kubota Y., Yamamoto A., Kiso M., Hasegawa A. Biological activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A. FEBS Lett. 1984 Feb 27;167(2):226–230. doi: 10.1016/0014-5793(84)80131-3. [DOI] [PubMed] [Google Scholar]
  14. Mizuno D., Yoshioka O., Akamatu M., Kataoka T. Antitumor effect of intracutaneous injection of bacterial lipopolysaccharide. Cancer Res. 1968 Aug;28(8):1531–1537. [PubMed] [Google Scholar]
  15. Morland B., Kaplan G. Macrophage activation in vivo and in vitro. Exp Cell Res. 1977 Sep;108(2):279–288. doi: 10.1016/s0014-4827(77)80035-9. [DOI] [PubMed] [Google Scholar]
  16. Morrison D. C., Ryan J. L. Bacterial endotoxins and host immune responses. Adv Immunol. 1979;28:293–450. doi: 10.1016/s0065-2776(08)60802-0. [DOI] [PubMed] [Google Scholar]
  17. Nikaido H., Nakae T. The outer membrane of Gram-negative bacteria. Adv Microb Physiol. 1979;20:163–250. doi: 10.1016/s0065-2911(08)60208-8. [DOI] [PubMed] [Google Scholar]
  18. Nishijima M., Bulawa C. E., Raetz C. R. Two interacting mutations causing temperature-sensitive phosphatidylglycerol synthesis in Escherichia coli membranes. J Bacteriol. 1981 Jan;145(1):113–121. doi: 10.1128/jb.145.1.113-121.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nishijima M., Raetz C. R. Characterization of two membrane-associated glycolipids from an Escherichia coli mutant deficient in phosphatidylglycerol. J Biol Chem. 1981 Oct 25;256(20):10690–10696. [PubMed] [Google Scholar]
  20. Nishijima M., Raetz C. R. Membrane lipid biogenesis in Escherichia coli: identification of genetic loci for phosphatidylglycerophosphate synthetase and construction of mutants lacking phosphatidylglycerol. J Biol Chem. 1979 Aug 25;254(16):7837–7844. [PubMed] [Google Scholar]
  21. North R. J. The concept of the activated macrophage. J Immunol. 1978 Sep;121(3):806–809. [PMC free article] [PubMed] [Google Scholar]
  22. Raetz C. R., Purcell S., Takayama K. Molecular requirements for B-lymphocyte activation by Escherichia coli lipopolysaccharide. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4624–4628. doi: 10.1073/pnas.80.15.4624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ralph P., Prichard J., Cohn M. Reticulum cell sarcoma: an effector cell in antibody-dependent cell-mediated immunity. J Immunol. 1975 Feb;114(2 Pt 2):898–905. [PubMed] [Google Scholar]
  24. Ray B. L., Painter G., Raetz C. R. The biosynthesis of gram-negative endotoxin. Formation of lipid A disaccharides from monosaccharide precursors in extracts of Escherichia coli. J Biol Chem. 1984 Apr 25;259(8):4852–4859. [PubMed] [Google Scholar]
  25. Rietschel E. T., Schade U., Jensen M., Wollenweber H. W., Lüderitz O., Greisman S. G. Bacterial endotoxins: chemical structure, biological activity and role in septicaemia. Scand J Infect Dis Suppl. 1982;31:8–21. [PubMed] [Google Scholar]
  26. Rosner M. R., Tang J., Barzilay I., Khorana H. G. Structure of the lipopolysaccharide from an Escherichia coli heptose-less mutant. I. Chemical degradations and identification of products. J Biol Chem. 1979 Jul 10;254(13):5906–5917. [PubMed] [Google Scholar]
  27. Schultz R. M., Papamatheakis J. D., Chirigos M. A. Interferon: an inducer of macrophage activation by polyanions. Science. 1977 Aug 12;197(4304):674–676. doi: 10.1126/science.877584. [DOI] [PubMed] [Google Scholar]
  28. Strain S. M., Fesik S. W., Armitage I. M. Characterization of lipopolysaccharide from a heptoseless mutant of Escherichia coli by carbon 13 nuclear magnetic resonance. J Biol Chem. 1983 Mar 10;258(5):2906–2910. [PubMed] [Google Scholar]
  29. Takayama K., Qureshi N., Mascagni P., Anderson L., Raetz C. R. Glucosamine-derived phospholipids in Escherichia coli. Structure and chemical modification of a triacyl glucosamine 1-phosphate found in a phosphatidylglycerol-deficient mutant. J Biol Chem. 1983 Dec 10;258(23):14245–14252. [PubMed] [Google Scholar]
  30. Takayama K., Qureshi N., Mascagni P. Complete structure of lipid A obtained from the lipopolysaccharides of the heptoseless mutant of Salmonella typhimurium. J Biol Chem. 1983 Nov 10;258(21):12801–12803. [PubMed] [Google Scholar]
  31. Takayama K., Qureshi N., Mascagni P., Nashed M. A., Anderson L., Raetz C. R. Fatty acyl derivatives of glucosamine 1-phosphate in Escherichia coli and their relation to lipid A. Complete structure of A diacyl GlcN-1-P found in a phosphatidylglycerol-deficient mutant. J Biol Chem. 1983 Jun 25;258(12):7379–7385. [PubMed] [Google Scholar]
  32. Takayama K., Qureshi N., Raetz C. R., Ribi E., Peterson J., Cantrell J. L., Pearson F. C., Wiggins J., Johnson A. G. Influence of fine structure of lipid A on Limulus amebocyte lysate clotting and toxic activities. Infect Immun. 1984 Aug;45(2):350–355. doi: 10.1128/iai.45.2.350-355.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Taniyama T., Holden H. T. Direct augmentation of cytolytic activity of tumor-derived macrophages and macrophage cell lines by muramyl dipeptide. Cell Immunol. 1979 Dec;48(2):369–374. doi: 10.1016/0008-8749(79)90131-x. [DOI] [PubMed] [Google Scholar]
  34. Weinberg J. B., Chapman H. A., Jr, Hibbs J. B., Jr Characterization of the effects of endotoxin on macrophage tumor cell killing. J Immunol. 1978 Jul;121(1):72–80. [PubMed] [Google Scholar]
  35. Wightman P. D., Raetz C. R. The activation of protein kinase C by biologically active lipid moieties of lipopolysaccharide. J Biol Chem. 1984 Aug 25;259(16):10048–10052. [PubMed] [Google Scholar]
  36. Wollenweber H. W., Broady K. W., Lüderitz O., Rietschel E. T. The chemical structure of lipid A. Demonstration of amide-linked 3-acyloxyacyl residues in Salmonella minnesota Re lipopolysaccharide. Eur J Biochem. 1982 May;124(1):191–198. doi: 10.1111/j.1432-1033.1982.tb05924.x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES