Logo of clinexpimmunolLink to Publisher's site
Clin Exp Immunol. 1989 May; 76(2): 240–245.
PMCID: PMC1541837

Lipoarabinomannan from Mycobacterium tuberculosis induces the production of tumour necrosis factor from human and murine macrophages.


We show here that purified lipoarabinomannan (LAM) from Mycobacterium tuberculosis can cause the release of tumour necrosis factor (TNF) in vitro from human blood monocytes and activated mouse peritoneal macrophages, and the production of TNF in vivo in mice pretreated with Propionibacterium acnes, with a potency comparable to that of lipopolysaccharide (LPS) from Gram negative bacteria. Like LPS, LAM binds to polymyxin B. We confirmed that its activity was distinct from any contaminating LPS and was associated with the antigenic activity by affinity chromatography, using a monoclonal antibody specific for LAM. Treatment with dilute alkali greatly diminished the TNF-inducing activity, suggesting that omicron-acyl groups may be involved. When LAM was fractionated by electrophoresis on SDS-Page and blotted on nitrocellulose, most TNF-inducing capacity coincided with the bulk of the LAM, as estimated by molecular weight and antigenic activity. This modification of the Western blotting technique may be generally useful for the study of macrophage-triggering molecules. The ability of LAM to cause the release of TNF may be responsible for some of the characteristics of tuberculosis, such as fever, weight loss, raised acute phase reactants and necrosis that can be mediated by this cytokine.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Andus T, Geiger T, Hirano T, Kishimoto T, Heinrich PC. Action of recombinant human interleukin 6, interleukin 1 beta and tumor necrosis factor alpha on the mRNA induction of acute-phase proteins. Eur J Immunol. 1988 May;18(5):739–746. [PubMed]
  • Bate CA, Taverne J, Playfair JH. Malarial parasites induce TNF production by macrophages. Immunology. 1988 Jun;64(2):227–231. [PMC free article] [PubMed]
  • Beutler B, Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986 Apr 17;320(6063):584–588. [PubMed]
  • Bomford R, Moreno C. Mechanism of the anti-tumour effect of glucans and fructosans: a comparison with C. parvum. Br J Cancer. 1977 Jul;36(1):41–48. [PMC free article] [PubMed]
  • Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. [PMC free article] [PubMed]
  • Dinarello CA, Cannon JG, Wolff SM, Bernheim HA, Beutler B, Cerami A, Figari IS, Palladino MA, Jr, O'Connor JV. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1433–1450. [PMC free article] [PubMed]
  • Gaylord H, Brennan PJ. Leprosy and the leprosy bacillus: recent developments in characterization of antigens and immunology of the disease. Annu Rev Microbiol. 1987;41:645–675. [PubMed]
  • Gaylord H, Brennan PJ, Young DB, Buchanan TM. Most Mycobacterium leprae carbohydrate-reactive monoclonal antibodies are directed to lipoarabinomannan. Infect Immun. 1987 Nov;55(11):2860–2863. [PMC free article] [PubMed]
  • Hunter SW, Gaylord H, Brennan PJ. Structure and antigenicity of the phosphorylated lipopolysaccharide antigens from the leprosy and tubercle bacilli. J Biol Chem. 1986 Sep 15;261(26):12345–12351. [PubMed]
  • Ivanyi J, Sinha S, Aston R, Cussell D, Keen M, Sengupta U. Definition of species specific and cross-reactive antigenic determinants of Mycobacterium leprae using monoclonal antibodies. Clin Exp Immunol. 1983 Jun;52(3):528–536. [PMC free article] [PubMed]
  • Jakobsen PH, Baek L, Jepsen S. Demonstration of soluble Plasmodium falciparum antigens reactive with Limulus amoebocyte lysate and polymyxin B. Parasite Immunol. 1988 Nov;10(6):593–606. [PubMed]
  • Meager A, Parti S, Leung H, Peil E, Mahon B. Preparation and characterization of monoclonal antibodies directed against antigenic determinants of recombinant human tumour necrosis factor (rTNF). Hybridoma. 1987 Jun;6(3):305–311. [PubMed]
  • Moreno C, Mehlert A, Lamb J. The inhibitory effects of mycobacterial lipoarabinomannan and polysaccharides upon polyclonal and monoclonal human T cell proliferation. Clin Exp Immunol. 1988 Nov;74(2):206–210. [PMC free article] [PubMed]
  • NETER E, WESTPHAL O, LUDERITZ O, GORZYNSKI EA, EICHENBERGER E. Studies of enterobacterial lipopolysaccharides; effects of heat and chemicals on erythrocyte-modifying, antigenic, toxic and pyrogenic properties. J Immunol. 1956 May;76(5):377–385. [PubMed]
  • O'BRIEN JR. Non-reactive tuberculosis. J Clin Pathol. 1954 Aug;7(3):216–225. [PMC free article] [PubMed]
  • Rook GA. Role of activated macrophages in the immunopathology of tuberculosis. Br Med Bull. 1988 Jul;44(3):611–623. [PubMed]
  • Rook GA, Taverne J, Leveton C, Steele J. The role of gamma-interferon, vitamin D3 metabolites and tumour necrosis factor in the pathogenesis of tuberculosis. Immunology. 1987 Oct;62(2):229–234. [PMC free article] [PubMed]
  • Rothstein JL, Schreiber H. Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice. Proc Natl Acad Sci U S A. 1988 Jan;85(2):607–611. [PMC free article] [PubMed]
  • Sibley LD, Hunter SW, Brennan PJ, Krahenbuhl JL. Mycobacterial lipoarabinomannan inhibits gamma interferon-mediated activation of macrophages. Infect Immun. 1988 May;56(5):1232–1236. [PMC free article] [PubMed]
  • Sugden EA, Samagh BS, Bundle DR, Duncan JR. Lipoarabinomannan and lipid-free arabinomannan antigens of Mycobacterium paratuberculosis. Infect Immun. 1987 Mar;55(3):762–770. [PMC free article] [PubMed]
  • Young D, Kent L, Rees A, Lamb J, Ivanyi J. Immunological activity of a 38-kilodalton protein purified from Mycobacterium tuberculosis. Infect Immun. 1986 Oct;54(1):177–183. [PMC free article] [PubMed]
  • Young DB, Lamb JR. T lymphocytes respond to solid-phase antigen: a novel approach to the molecular analysis of cellular immunity. Immunology. 1986 Oct;59(2):167–171. [PMC free article] [PubMed]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...