Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Apr;64(4):1491–1493. doi: 10.1128/iai.64.4.1491-1493.1996

Calixarenes with host-mediated potency in experimental tuberculosis: further evidence that macrophage lipids are involved in their mechanism of action.

P D Hart 1, J A Armstrong 1, E Brodaty 1
PMCID: PMC173952  PMID: 8606127

Abstract

Some time ago, it was found that attachment of hydrophilic polyoxyethylene chains to various hydrophobic phenols and alcohols gave water-soluble products which, although inactive in vitro, influenced and experimental tuberculous infection. With short chains the infection was suppressed, and with long chains it was promoted. Later work concentrated on Macrocyclon (short chain) and HOC-60 (long chain), both derived from a hydrophobic, polyphenolic calixarene. Growth of Mycobacterium tuberculosis inside macrophages (M phi) was inhibited by Macrocyclon and stimulated by HOC-60. Also, triglyceride lipase from M phi extracts and an extracellular phospholipase were inhibited by Macrocyclon and stimulated by HOC-60. This suggestion of a mechanism has been strengthened by the finding that M phi cultivated in monolayers and treated with Macrocyclon showed accumulation of lipid and little formation of fatty acid after incubation of killed cells. With HOC-60, lipid was depleted and much fatty acid was found.

Full Text

The Full Text of this article is available as a PDF (723.3 KB).

Selected References

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

  1. Armstrong J. A., Hart P. D. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med. 1971 Sep 1;134(3 Pt 1):713–740. doi: 10.1084/jem.134.3.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. CORNFORTH J. W., HART P. D., NICHOLLS G. A., REES R. J., STOCK J. A. Antituberculous effects of certain surface-active polyoxyethylene ethers. Br J Pharmacol Chemother. 1955 Mar;10(1):73–88. doi: 10.1111/j.1476-5381.1955.tb00063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carter R. L., Birbeck M. S., Stock J. A. Lysosomal changes and enhanced metastatic growth: an experimental study of the effects of some non-ionic surfactants. Int J Cancer. 1971 Jan 15;7(1):34–49. doi: 10.1002/ijc.2910070105. [DOI] [PubMed] [Google Scholar]
  4. Hart P. D., Gordon A. H. Suggested role of lysosomal lipid in the contrasting effects of 'triton WR-1339' and dextran on tuberculous infection. Nature. 1969 May 17;222(5194):672–673. doi: 10.1038/222672a0. [DOI] [PubMed] [Google Scholar]
  5. Hart P. D. Mycobacterium tuberculosis in macrophages: effect of certain surfactants and other membrane-active compounds. Science. 1968 Nov 8;162(3854):686–689. doi: 10.1126/science.162.3854.686. [DOI] [PubMed] [Google Scholar]
  6. Hart P. D., Payne S. N. Effects of non-ionic surfactants that modify experimental tuberculosis on lipase activity of macrophages. Br J Pharmacol. 1971 Sep;43(1):190–196. doi: 10.1111/j.1476-5381.1971.tb07168.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hart P. D., Young M. R. Ammonium chloride, an inhibitor of phagosome-lysosome fusion in macrophages, concurrently induces phagosome-endosome fusion, and opens a novel pathway: studies of a pathogenic mycobacterium and a nonpathogenic yeast. J Exp Med. 1991 Oct 1;174(4):881–889. doi: 10.1084/jem.174.4.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jain M. K., Jahagirdar D. V. Effect of antituberculous calixarenes on phospholipase A2 susceptibility and on fusion of phospholipid bilayers. Biochem J. 1985 May 1;227(3):789–794. doi: 10.1042/bj2270789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. LOVELOCK J. E., REES R. J. Possible site and mode of action of certain lipotropic macromolecules in tuberculosis. Nature. 1955 Jan 22;175(4447):161–163. doi: 10.1038/175161a0. [DOI] [PubMed] [Google Scholar]
  10. Mackenzie C. G., Mackenzie J. B., Reiss O. K. Regulation of cell lipid metabolism and accumulation. V. Quantitative and structural aspects of triglyceride accumulation caused by lipogenic substances. Wistar Inst Symp Monogr. 1967;6:63–83. [PubMed] [Google Scholar]
  11. Moskowitz M. S., Moskowitz A. A. Lipase: Localization in Adipose Tissue. Science. 1965 Jul 2;149(3679):72–73. doi: 10.1126/science.149.3679.72. [DOI] [PubMed] [Google Scholar]
  12. Yui S., Yamazaki M. Neutral lipid accumulation in macrophages during lipid-induced macrophage growth. J Leukoc Biol. 1989 Mar;45(3):189–197. doi: 10.1002/jlb.45.3.189. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES