Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 Jan;36(1):39–45. doi: 10.1128/aac.36.1.39

Lipid complexing decreases amphotericin B inflammatory activation of human neutrophils compared with that of a desoxycholate-suspended preparation of amphotericin B (Fungizone).

G W Sullivan 1, H T Carper 1, G L Mandell 1
PMCID: PMC189222  PMID: 1590697

Abstract

Amphotericin B (AmB) has toxic effects and alters neutrophil (polymorphonuclear leukocyte [PMN]) function. A lipid-complexed formulation of AmB (AmB-LC) has been reported (A. S. Janoff, L. T. Boni, M. C. Popescu, S. R. Minchey, P. R. Cullis, T. D. Madden, T. Taraschi, S. M. Gruner, E. Shyamsunder, M. W. Tate, R. Mendelsohn, and D. Bonner, Proc. Natl. Acad. Sci. USA 85:6122-6126, 1988) to be less toxic than a desoxycholate-suspended preparation of AmB (AmB-des; Fungizone). In this study we compared the effects of AmB-des and AmB-LC on in vitro PMN function. Neither form of AmB stimulated PMN chemiluminescence, but AmB-des (2 micrograms/ml) nearly tripled PMN chemiluminescence in response to f-Met-Leu-Phe (fMLP), a phenomenon known as priming. Because AmB stimulates monocytes to release cytokines which can affect PMN function, we studied the effects of AmB on PMNs in mixed leukocyte cultures. AmB-des (1 to 2 micrograms/ml) increased the chemiluminescence of PMNs plus mixed mononuclear leukocytes (MNLs) to fMLP. The activity was about three times that of PMNs plus MNLs and seven times the activity of PMNs stimulated with fMLP in the absence of MNLs. Cell-free AmB-des (2 micrograms/ml)-stimulated, MNL-conditioned medium primed pure PMNs to a level equal to that of whole MNLs treated with AmB-des. AmB-LC was much less potent. AmB-LC (20 micrograms/ml) increased fMLP-stimulated chemiluminescence to two times that of PMNs plus MNLs without AmB-LC. AmB-des (2 micrograms/ml) (but not AmB-LC [2 micrograms/ml]) increased nitroblue tetrazolium reduction by PMNs in whole blood from 31 to 52% of positive cells. Neither form of AmB increased Mac-1 (the CD11b/CD18 integrin) expression of pure PMNs. AmB-des (0.5 to 2 micrograms/ml) (but not AmB-LC [< or = 40 micrograms/ml]) nearly doubled PMN Mac-1 expression in the presence of MNLs, and cell-free AmB-des (2 micrograms/ml)-stimulated, MNL-conditioned medium stimulated PMN Mac-1 to 125% of the control level. AmB-des (0.2 to 2 micrograms/ml) (but not AmB-LC [< or = 40 micrograms/ml]) decreased chemotaxis of pure PMNs to fMLP by as much as 35% and that of PMNs in the presence of MNLs by as much as 50%. Desoxycholate by itself had no effect on PMN function. These differences in activity between AmB-des and AmB-LC may explain the lessened toxicity observed with AmB-LC.

Full text

PDF
39

Images in this article

42Image
on p.42

Selected References

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

  1. Allen R. C., Loose L. D. Phagocytic activation of a luminol-dependent chemiluminescence in rabbit alveolar and peritoneal macrophages. Biochem Biophys Res Commun. 1976 Mar 8;69(1):245–252. doi: 10.1016/s0006-291x(76)80299-9. [DOI] [PubMed] [Google Scholar]
  2. Baehner R. L., Nathan D. G. Quantitative nitroblue tetrazolium test in chronic granulomatous disease. N Engl J Med. 1968 May 2;278(18):971–976. doi: 10.1056/NEJM196805022781801. [DOI] [PubMed] [Google Scholar]
  3. Björkstén B., Ray C., Quie P. G. Inhibition of human neutrophil chemotaxis and chemiluminescence by amphotericin B. Infect Immun. 1976 Jul;14(1):315–317. doi: 10.1128/iai.14.1.315-317.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brajtburg J., Elberg S., Kobayashi G. S., Medoff G. Inhibition of amphotericin B (Fungizone) toxicity to cells by egg lecithin-glycocholic acid mixed micelles. Antimicrob Agents Chemother. 1990 Dec;34(12):2415–2416. doi: 10.1128/aac.34.12.2415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brajtburg J., Powderly W. G., Kobayashi G. S., Medoff G. Amphotericin B: current understanding of mechanisms of action. Antimicrob Agents Chemother. 1990 Feb;34(2):183–188. doi: 10.1128/aac.34.2.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chapman H. A., Jr, Hibbs J. B., Jr Modulation of macrophage tumoricidal capability by polyene antibiotics: support for membrane lipid as a regulatory determinant of macrophage function. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4349–4353. doi: 10.1073/pnas.75.9.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cheson B. D., Christensen R. L., Sperling R., Kohler B. E., Babior B. M. The origin of the chemiluminescence of phagocytosing granulocytes. J Clin Invest. 1976 Oct;58(4):789–796. doi: 10.1172/JCI108530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chia J. K., Pollack M. Amphotericin B induces tumor necrosis factor production by murine macrophages. J Infect Dis. 1989 Jan;159(1):113–116. doi: 10.1093/infdis/159.1.113. [DOI] [PubMed] [Google Scholar]
  9. Chunn C. J., Starr P. R., Gilbert D. N. Neutrophil toxicity of amphotericin B. Antimicrob Agents Chemother. 1977 Aug;12(2):226–230. doi: 10.1128/aac.12.2.226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clark J. M., Whitney R. R., Olsen S. J., George R. J., Swerdel M. R., Kunselman L., Bonner D. P. Amphotericin B lipid complex therapy of experimental fungal infections in mice. Antimicrob Agents Chemother. 1991 Apr;35(4):615–621. doi: 10.1128/aac.35.4.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dahm L. J., Roth R. A. Differential effects of lithocholate on rat neutrophil activation. J Leukoc Biol. 1990 Jun;47(6):551–560. doi: 10.1002/jlb.47.6.551. [DOI] [PubMed] [Google Scholar]
  12. Fast D. J., Schlievert P. M., Nelson R. D. Nonpurulent response to toxic shock syndrome toxin 1-producing Staphylococcus aureus. Relationship to toxin-stimulated production of tumor necrosis factor. J Immunol. 1988 Feb 1;140(3):949–953. [PubMed] [Google Scholar]
  13. Ferrante A., Thong Y. H. Optimal conditions for simultaneous purification of mononuclear and polymorphonuclear leucocytes from human blood by the Hypaque-Ficoll method. J Immunol Methods. 1980;36(2):109–117. doi: 10.1016/0022-1759(80)90036-8. [DOI] [PubMed] [Google Scholar]
  14. Janoff A. S., Boni L. T., Popescu M. C., Minchey S. R., Cullis P. R., Madden T. D., Taraschi T., Gruner S. M., Shyamsunder E., Tate M. W. Unusual lipid structures selectively reduce the toxicity of amphotericin B. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6122–6126. doi: 10.1073/pnas.85.16.6122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kan V. L., Bennett J. E., Amantea M. A., Smolskis M. C., McManus E., Grasela D. M., Sherman J. W. Comparative safety, tolerance, and pharmacokinetics of amphotericin B lipid complex and amphotericin B desoxycholate in healthy male volunteers. J Infect Dis. 1991 Aug;164(2):418–421. doi: 10.1093/infdis/164.2.418. [DOI] [PubMed] [Google Scholar]
  16. Lin S. H., Medoff G., Kobayashi G. S. Effects of amphotericin B on macrophages and their precursor cells. Antimicrob Agents Chemother. 1977 Jan;11(1):154–160. doi: 10.1128/aac.11.1.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lohr K. M., Snyderman R. Amphotericin B alters the affinity and functional activity of the oligopeptide chemotactic factor receptor on human polymorphonuclear leukocytes. J Immunol. 1982 Oct;129(4):1594–1599. [PubMed] [Google Scholar]
  18. Lopez-Berestein G., Mehta R., Hopfer R. L., Mills K., Kasi L., Mehta K., Fainstein V., Luna M., Hersh E. M., Juliano R. Treatment and prophylaxis of disseminated infection due to Candida albicans in mice with liposome-encapsulated amphotericin B. J Infect Dis. 1983 May;147(5):939–945. doi: 10.1093/infdis/147.5.939. [DOI] [PubMed] [Google Scholar]
  19. Marmer D. J., Fields B. T., Jr, France G. L., Steele R. W. Ketoconazole, amphotericin B, and amphotericin B methyl ester: comparative in vitro and in vivo toxicological effects on neutrophil function. Antimicrob Agents Chemother. 1981 Nov;20(5):660–665. doi: 10.1128/aac.20.5.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nelson R. D., Quie P. G., Simmons R. L. Chemotaxis under agarose: a new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes. J Immunol. 1975 Dec;115(6):1650–1656. [PubMed] [Google Scholar]
  21. Ochs H. D., Igo R. P. The NBT slide test: a simple screening method for detecting chronic granulomatous disease and female carriers. J Pediatr. 1973 Jul;83(1):77–82. doi: 10.1016/s0022-3476(73)80316-6. [DOI] [PubMed] [Google Scholar]
  22. Otsuka Y., Nagano K., Nagano K., Hori K., Oh-ishi J., Hayashi H., Watanabe N., Niitsu Y. Inhibition of neutrophil migration by tumor necrosis factor. Ex vivo and in vivo studies in comparison with in vitro effect. J Immunol. 1990 Oct 15;145(8):2639–2643. [PubMed] [Google Scholar]
  23. Perfect J. R., Granger D. L., Durack D. T. Effects of antifungal agents and gamma interferon on macrophage cytotoxicity for fungi and tumor cells. J Infect Dis. 1987 Aug;156(2):316–323. doi: 10.1093/infdis/156.2.316. [DOI] [PubMed] [Google Scholar]
  24. Pichyangkul S., Schick D., Schober W., Dixon G., Khan A. Increased expression of adhesive proteins on leukocytes by TNF alpha. Exp Hematol. 1988 Aug;16(7):588–593. [PubMed] [Google Scholar]
  25. Pisarik L., Joly V., Jullien S., Carbon C., Yeni P. Reduction of free amphotericin B acute toxicity in mice after intravenous administration of empty liposomes. J Infect Dis. 1990 May;161(5):1042–1044. doi: 10.1093/infdis/161.5.1042. [DOI] [PubMed] [Google Scholar]
  26. Shalaby M. R., Palladino M. A., Jr, Hirabayashi S. E., Eessalu T. E., Lewis G. D., Shepard H. M., Aggarwal B. B. Receptor binding and activation of polymorphonuclear neutrophils by tumor necrosis factor-alpha. J Leukoc Biol. 1987 Mar;41(3):196–204. doi: 10.1002/jlb.41.3.196. [DOI] [PubMed] [Google Scholar]
  27. Sullivan G. W., Carper H. T., Sullivan J. A., Murata T., Mandell G. L. Both recombinant interleukin-1 (beta) and purified human monocyte interleukin-1 prime human neutrophils for increased oxidative activity and promote neutrophil spreading. J Leukoc Biol. 1989 May;45(5):389–395. doi: 10.1002/jlb.45.5.389. [DOI] [PubMed] [Google Scholar]
  28. Supapidhayakul S. R., Kizlaitis L. R., Andersen B. R. Stimulation of human and canine neutrophil metabolism by amphotericin B. Antimicrob Agents Chemother. 1981 Feb;19(2):284–289. doi: 10.1128/aac.19.2.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wilson E., Thorson L., Speert D. P. Enhancement of macrophage superoxide anion production by amphotericin B. Antimicrob Agents Chemother. 1991 May;35(5):796–800. doi: 10.1128/aac.35.5.796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wolf J. E., Massof S. E. In vivo activation of macrophage oxidative burst activity by cytokines and amphotericin B. Infect Immun. 1990 May;58(5):1296–1300. doi: 10.1128/iai.58.5.1296-1300.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yasui K., Masuda M., Matsuoka T., Yamazaki M., Komiyama A., Akabane T., Murata K. Miconazole and amphotericin B alter polymorphonuclear leukocyte functions and membrane fluidity in similar fashions. Antimicrob Agents Chemother. 1988 Dec;32(12):1864–1868. doi: 10.1128/aac.32.12.1864. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES