Abstract
We have examined the effects of the sterol-binding polyene antibiotics on macrophage tumoricidal capability. Incubation for 2 hr of activated macrophages from bacillus Calmette-Guérin-infected mice with amphotericin B at 0.5--2 microgram/ml or amphotericin B methyl ester at 0.5--10 microgram/ml enhanced the capability of activated macrophages to kill 3T12 cells. These polyenes did not make normal or stimulated macrophages tumoricidal. Experiments with the ionophores gramicidin, alamethecin, nigericin, and valinomycin indicate that the ionophoretic properties of amphotericin B may not account for its enhancing effect on macrophage tumoricidal potential. Two polyenes with a smaller ring structure, filipin and pimaricin, were also ineffective suggesting that stereospecific modifications in membrane lipid organization underlie the enhancing effect of amphotericin B. The results suggest that the clinical efficacy of amphotericin B in promoting resistance to fungal disease and possibly to neoplasia may operate in part through potentiation of macrophage effector functions.
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- Bruckdorfer K. R., Demel R. A., De Gier J., van Deenen L. L. The effect of partial replacements of membrane cholesterol by other steroids on the osmotic fragility and glycerol permeability of erythrocytes. Biochim Biophys Acta. 1969 Jul 15;183(2):334–345. doi: 10.1016/0005-2736(69)90089-3. [DOI] [PubMed] [Google Scholar]
- Chapman H. A., Jr, Hibbs J. B., Jr Modulation of macrophage tumoricidal capability by components of normal serum: a central role for lipid. Science. 1977 Jul 15;197(4300):282–285. doi: 10.1126/science.195338. [DOI] [PubMed] [Google Scholar]
- Dennis V. W., Stead N. W., Andreoli T. E. Molecular aspects of polyene- and sterol-dependent pore formation in thin lipid membranes. J Gen Physiol. 1970 Mar;55(3):375–400. doi: 10.1085/jgp.55.3.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dos Reis G. A., Oliveira-Castro G. M. Electrophysiology of phagocytic membranes. I. Potassium-dependent slow membrane hyperpolarizations in mice macrophages. Biochim Biophys Acta. 1977 Sep 19;469(3):257–263. doi: 10.1016/0005-2736(77)90161-4. [DOI] [PubMed] [Google Scholar]
- Evans R. Macrophages in syngeneic animal tumours. Transplantation. 1972 Oct;14(4):468–473. doi: 10.1097/00007890-197210000-00011. [DOI] [PubMed] [Google Scholar]
- Fidler I. J. Activation in vitro of mouse macrophages by syngeneic, allogeneic, or xenogeneic lymphocyte supernatants. J Natl Cancer Inst. 1975 Nov;55(5):1159–1163. doi: 10.1093/jnci/55.5.1159. [DOI] [PubMed] [Google Scholar]
- Hibbs J. B., Jr, Lambert L. H., Jr, Remington J. S. Possible role of macrophage mediated nonspecific cytotoxicity in tumour resistance. Nat New Biol. 1972 Jan 12;235(54):48–50. doi: 10.1038/newbio235048a0. [DOI] [PubMed] [Google Scholar]
- Hibbs J. B., Jr, Taintor R. R., Chapman H. A., Jr, Weinberg J. B. Macrophage tumor killing: influence of the local environment. Science. 1977 Jul 15;197(4300):279–282. doi: 10.1126/science.327547. [DOI] [PubMed] [Google Scholar]
- Hladky S. B., Haydon D. A. Ion transfer across lipid membranes in the presence of gramicidin A. I. Studies of the unit conductance channel. Biochim Biophys Acta. 1972 Aug 9;274(2):294–312. doi: 10.1016/0005-2736(72)90178-2. [DOI] [PubMed] [Google Scholar]
- Hoeprich P. D., Huston A. C. Susceptibility of coccidioides immitis, Candida albicans, and Cryptococcus neoformans to amphotericin B, flucytosine, and clotrimazole. J Infect Dis. 1975 Aug;132(2):133–141. doi: 10.1093/infdis/132.2.133. [DOI] [PubMed] [Google Scholar]
- Hsuchen C. C., Feingold D. S. Selective membrane toxicity of the polyene antibiotics: studies on lecithin membrane models (liposomes). Antimicrob Agents Chemother. 1973 Sep;4(3):309–315. doi: 10.1128/aac.4.3.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kleemann W., McConnell H. M. Interactions of proteins and cholesterol with lipids in bilayer membranes. Biochim Biophys Acta. 1976 Jan 21;419(2):206–222. doi: 10.1016/0005-2736(76)90347-3. [DOI] [PubMed] [Google Scholar]
- Kobayashi G. S., Medoff G. Antifungal agents: recent developments. Annu Rev Microbiol. 1977;31:291–308. doi: 10.1146/annurev.mi.31.100177.001451. [DOI] [PubMed] [Google Scholar]
- Kotler-Brajtburg J., Medoff G., Kobayashi G. S., Schlessinger D. Sensitivity to amphotericin B and the cholesterol: phospholipid molar ratios of 3T3, L, BHK and HeLa cells. Biochem Pharmacol. 1977 Apr 15;26(8):705–710. doi: 10.1016/0006-2952(77)90212-x. [DOI] [PubMed] [Google Scholar]
- Levin J., Tomasulo P. A., Oser R. S. Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med. 1970 Jun;75(6):903–911. [PubMed] [Google Scholar]
- Medoff G., Valeriote F., Lynch R. G., Schlessinger D., Kobayashi G. S. Synergistic effect of amphotericin B and 1,3-bis(2-chloroethyl)-1-nitrosourea against a transplantable AKR leukemia. Cancer Res. 1974 May;34(5):974–978. [PubMed] [Google Scholar]
- Mueller P., Rudin D. O. Action potentials induced in biomolecular lipid membranes. Nature. 1968 Feb 24;217(5130):713–719. doi: 10.1038/217713a0. [DOI] [PubMed] [Google Scholar]
- Papahadjopoulos D., Moscarello M., Eylar E. H., Isac T. Effects of proteins on thermotropic phase transitions of phospholipid membranes. Biochim Biophys Acta. 1975 Sep 2;401(3):317–335. doi: 10.1016/0005-2736(75)90233-3. [DOI] [PubMed] [Google Scholar]
- Piessens W. F., Churchill W. H., Jr, David Macrophages activated in vitro with lymphocyte mediators kill neoplastic but not normal cells. J Immunol. 1975 Jan;114(1 Pt 2):293–299. [PubMed] [Google Scholar]
- Presant C. A., Klahr C., Santala R. Amphotericin B induction of sensitivity to adriamycin, 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) plus cyclophosphamide in human neoplasia. Ann Intern Med. 1977 Jan;86(1):47–51. doi: 10.7326/0003-4819-86-1-47. [DOI] [PubMed] [Google Scholar]
- Pressman B. C. Ionophorous antibiotics as models for biological transport. Fed Proc. 1968 Nov-Dec;27(6):1283–1288. [PubMed] [Google Scholar]
- Reijngoud D. J., Oud P. S., Tager J. M. Effect of ionophores on intralysosomal pH. Biochim Biophys Acta. 1976 Oct 5;448(2):303–313. doi: 10.1016/0005-2736(76)90244-3. [DOI] [PubMed] [Google Scholar]
- Rudnick G. Active transport of 5-hydroxytryptamine by plasma membrane vesicles isolated from human blood platelets. J Biol Chem. 1977 Apr 10;252(7):2170–2174. [PubMed] [Google Scholar]
- Stein O., Vanderhoek J., Stein Y. Cholesterol content and sterol synthesis in human skin fibroblasts and rat aortic smooth muscle cells exposed to lipoprotein-depleted serum and high density apolipoprotein/phospholipid mixtures. Biochim Biophys Acta. 1976 May 27;431(2):347–358. doi: 10.1016/0005-2760(76)90155-7. [DOI] [PubMed] [Google Scholar]
- Stewart C. C., Lin H. S., Adles C. Proliferation and colony-forming ability of peritoneal exudate cells in liquid culture. J Exp Med. 1975 May 1;141(5):1114–1132. doi: 10.1084/jem.141.5.1114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valeriote F., Lynch R., Medoff G., Kumar B. V. Protective effects of amphotericin B against spontaneous and transplantable murine tumors. J Natl Cancer Inst. 1976 Mar;56(3):557–560. doi: 10.1093/jnci/56.3.557. [DOI] [PubMed] [Google Scholar]
- Wood G. W., Gollahon K. A. Detection and quantitation of macrophage infiltration into primary human tumors with the use of cell-surface markers. J Natl Cancer Inst. 1977 Oct;59(4):1081–1087. doi: 10.1093/jnci/59.4.1081. [DOI] [PubMed] [Google Scholar]
- de Kruijff B., Demel R. A. Polyene antibiotic-sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. 3. Molecular structure of the polyene antibiotic-cholesterol complexes. Biochim Biophys Acta. 1974 Feb 26;339(1):57–70. doi: 10.1016/0005-2736(74)90332-0. [DOI] [PubMed] [Google Scholar]
- de Kruijff B., Gerritsen W. J., Oerlemans A., Demel R. A., van Deenen L. L. Polyene antibiotic-sterol interactions in membranes of Acholeplasma laidlawii cells and lecithin liposomes. I. Specificity of the membrane permeability changes induced by the polyene antibiotics. Biochim Biophys Acta. 1974 Feb 26;339(1):30–43. doi: 10.1016/0005-2736(74)90330-7. [DOI] [PubMed] [Google Scholar]
- de Kruijff B., Gerritsen W. J., Oerlemans A., van Dijck P. W., Demel R. A., van Deenen L. L. Polyene antibiotic-sterol interactions in membranes of Acholesplasma laidlawii cells and lecithin liposomes. II. Temperature dependence of the polyene antibiotic-sterol complex formation. Biochim Biophys Acta. 1974 Feb 26;339(1):44–56. doi: 10.1016/0005-2736(74)90331-9. [DOI] [PubMed] [Google Scholar]