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. 1995 Jan;4(1):25–30. doi: 10.1155/S0962935195000056

Macrophage activation by lipopolysaccharide, interferon-γ and interleukin-4: effect of fatty acid metabolism

H Darmani 1, J L Harwood 2, J Parton 1, S K Jackson 1,✉
PMCID: PMC2365606  PMID: 18475612

Abstract

The aim of this study was to investigate the effects of interferon-γ and -β (IFN-γ, -β), interleukin-4 and -10 (IL-4, -10) and Hpopolysaccharide (LPS) on the metabolism and composition of phospholipid fatty acids in macrophages. Murine J774.2 macrophages were incubated with radiolabelled fatty acids and the appropriate stimulus and the incorporation and composition of the phospholipid classes was determined. IFN-γ and IL-4 specifically stimulated enhanced incorporation of [14C]-linoleic acid into the phosphatidytethanolamine fraction. IL-4 (in contrast to IFN-γ and LPS) reduced incorporation of [14C]- arachidonic acid into phosphatidylinositol. Incubation of J774.2 cells with linoleic acid significantly increased TNFα and nitric oxide production; arachidonic acid enhanced TNFα production but reduced nitric oxide production. It is concluded that IFN-γ, IL-4 and IL-10 may differentially regulate macrophage activation via effects on the metabolism of polyunsaturated fatty acids.

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Selected References

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  1. Akagawa K. S., Tokunaga T. Lack of binding of bacterial lipopolysaccharide to mouse lung macrophages and restoration of binding by gamma interferon. J Exp Med. 1985 Nov 1;162(5):1444–1459. doi: 10.1084/jem.162.5.1444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  3. Billiau A., Heremans H., Vandekerckhove F., Dillen C. Anti-interferon-gamma antibody protects mice against the generalized Shwartzman reaction. Eur J Immunol. 1987 Dec;17(12):1851–1854. doi: 10.1002/eji.1830171228. [DOI] [PubMed] [Google Scholar]
  4. Boraschi D., Censini S., Tagliabue A. Interferon-gamma reduces macrophage-suppressive activity by inhibiting prostaglandin E2 release and inducing interleukin 1 production. J Immunol. 1984 Aug;133(2):764–768. [PubMed] [Google Scholar]
  5. Cunha F. Q., Moncada S., Liew F. Y. Interleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by interferon-gamma in murine macrophages. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1155–1159. doi: 10.1016/0006-291x(92)91852-h. [DOI] [PubMed] [Google Scholar]
  6. Darmani H., Harwood J. L., Jackson S. K. Interferon-gamma-stimulated uptake and turnover of linoleate and arachidonate in macrophages: a possible pathway for hypersensitivity to endotoxin. Cell Immunol. 1993 Nov;152(1):59–71. doi: 10.1006/cimm.1993.1267. [DOI] [PubMed] [Google Scholar]
  7. Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. GARBUS J., DELUCA H. F., LOOMANS M. E., STRONG F. M. The rapid incorporation of phosphate into mitochondrial lipids. J Biol Chem. 1963 Jan;238:59–63. [PubMed] [Google Scholar]
  9. Gajewski T. F., Fitch F. W. Differential activation of murine TH1 and TH2 clones. Res Immunol. 1991 Jan;142(1):19–23. doi: 10.1016/0923-2494(91)90005-4. [DOI] [PubMed] [Google Scholar]
  10. Heinzel F. P., Sadick M. D., Holaday B. J., Coffman R. L., Locksley R. M. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989 Jan 1;169(1):59–72. doi: 10.1084/jem.169.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jackson S. K., Darmani H., Stark J. M., Harwood J. L. Interferon-gamma increases macrophage phospholipid polyunsaturation: a possible mechanism of endotoxin sensitivity. Int J Exp Pathol. 1992 Dec;73(6):783–791. [PMC free article] [PubMed] [Google Scholar]
  12. Jackson S. K., Stark J. M., Taylor S., Harwood J. L. Changes in phospholipid fatty acid composition and triacylglycerol content in mouse tissues after infection with bacille Calmette-Guérin. Br J Exp Pathol. 1989 Aug;70(4):435–441. [PMC free article] [PubMed] [Google Scholar]
  13. Katschinski T., Galanos C., Coumbos A., Freudenberg M. A. Gamma interferon mediates Propionibacterium acnes-induced hypersensitivity to lipopolysaccharide in mice. Infect Immun. 1992 May;60(5):1994–2001. doi: 10.1128/iai.60.5.1994-2001.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kunkel S. L., Chensue S. W. Arachidonic acid metabolites regulate interleukin-1 production. Biochem Biophys Res Commun. 1985 Apr 30;128(2):892–897. doi: 10.1016/0006-291x(85)90130-5. [DOI] [PubMed] [Google Scholar]
  15. Kunkel S. L., Spengler M., May M. A., Spengler R., Larrick J., Remick D. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem. 1988 Apr 15;263(11):5380–5384. [PubMed] [Google Scholar]
  16. Mosmann T. R., Coffman R. L. Heterogeneity of cytokine secretion patterns and functions of helper T cells. Adv Immunol. 1989;46:111–147. doi: 10.1016/s0065-2776(08)60652-5. [DOI] [PubMed] [Google Scholar]
  17. SUTER E., KIRSANOW E. M. Hyperreactivity to endotoxin in mice infected with mycobacteria. Induction and elicitation of the reactions. Immunology. 1961 Oct;4:354–365. [PMC free article] [PubMed] [Google Scholar]
  18. Schade U. F., Engel R., Jakobs D. Differential protective activities of site specific lipoxygenase inhibitors in endotoxic shock and production of tumor necrosis factor. Int J Immunopharmacol. 1991;13(5):565–571. doi: 10.1016/0192-0561(91)90077-k. [DOI] [PubMed] [Google Scholar]
  19. Schade U. F. Involvement of lipoxygenases in the activation of mouse macrophages by endotoxin. Biochem Biophys Res Commun. 1986 Jul 31;138(2):842–849. doi: 10.1016/s0006-291x(86)80573-3. [DOI] [PubMed] [Google Scholar]
  20. Scott P., Natovitz P., Coffman R. L., Pearce E., Sher A. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988 Nov 1;168(5):1675–1684. doi: 10.1084/jem.168.5.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stark J. M., Jackson S. K. Sensitivity to endotoxin is induced by increased membrane fatty-acid unsaturation and oxidant stress. J Med Microbiol. 1990 Aug;32(4):217–221. doi: 10.1099/00222615-32-4-217. [DOI] [PubMed] [Google Scholar]
  22. Suk K., Somers S. D., Erickson K. L. Regulation of murine macrophage function by IL-4: IL-4 and IFN-gamma differentially regulate macrophage tumoricidal activation. Immunology. 1993 Dec;80(4):617–624. [PMC free article] [PubMed] [Google Scholar]

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