Abstract
We recently reported that some lipid species of cell membranes and lipoproteins induced the growth of peripheral macrophages. In this study, the effects of phospholipids on tumor necrosis factor (TNF)‐releasing activity of macrophages were examined. Ten to 20 μg/ml of cardiolipin, which is a suboptimal concentration for macrophage growth‐stimulation, augmented macrophage TNF release triggered by lipopolysaccharide (LPS) in vitro. This priming effect appeared with 1 day of preincubation and was still potent on day 3, whereas the priming effect of interferon‐γ (IFN‐γ) peaked at 3 h and then gradually decreased. In contrast, a high concentration of cardiolipin (40 μg/ml) which is optimal for the induction of macrophage growth, completely suppressed LPS‐triggered TNF release from not only untreated macrophages but also IFN‐γ‐primed macrophages. The suppressive effect was potent even with 3 h preincubation, was still potent on day 3, and was not abolished by indomethacin. Cardiolipin had scarcely any effect on the triggering activity of LPS. Similar augmentative and suppressive activities were observed in peroxidized phosphatidylserine, which is also highly active in inducing macrophage growth, but was not found in native phosphatidylserine, which is less active, nor in phosphatidylcholine, which is an inactive species toward macrophage growth. These results suggest that lipids may be important endogenous factors in regulating both activation and growth states of peripheral macrophages.
Keywords: Macrophage, Tumor necrosis factor release, Phospholipid
Full Text
The Full Text of this article is available as a PDF (458.0 KB).
REFERENCES
- 1. ) Hibbs , J. B. , Jr. , Taintor , R. R. , Chapman , H. A. , Jr. and Weinberg , J. B.Macrophage tumor killing: influence of the local environment . Science , 197 , 279 – 282 ( 1977. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Adams , D. O. and Hamilton , T. A.The cell biology of macrophage activation . Ann, Rev. Immunol , 2 , 283 – 318 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Yui , S. , Mizuno , D. and Yamazaki , M.Induction of macrophage growth by the lipid moiety of lipoprotein and its augmentation by denaturation of the lipoproteins . J. Leukocyte Biol. , 38 , 697 – 707 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Yui , S. and Yamazaki , M.Induction of macrophage growth by effete cells . J. Leukocyte Biol. , 39 , 489 – 497 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Yui , S. and Yamazaki , M.Induction of macrophage growth by lipids . J. Immunol. , 136 , 1334 – 1338 ( 1986. ). [PubMed] [Google Scholar]
- 6. ) Yui , S. and Yamazaki , M.Induction of macrophage growth by negatively charged phospholipids . J. Leukocyte Biol. , 39 , 713 – 716 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Yui , S. and Yamazaki , M.Relationship of ability of phospholipids to stimulate growth and bind to macrophages . J. Leukocyte Biol. , 41 , 392 – 399 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Yui , S. and Yamazaki , M.Augmentation of macrophage growth‐stimulating activity of lipids by their peroxidation . J. Immunol. , 144 , 1466 – 1471 ( 1990. ). [PubMed] [Google Scholar]
- 9. ) Stanley , E. R. , Cifone , M. , Heard , P. M. and Difendi , V.Factors regulating macrophage production and growth: identity of colony stimulating factor and macrophage growth factor . J. Exp. Med. , 143 , 631 – 647 ( 1976. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Stewart , C. C. and Lin , H‐S.Macrophage growth factor and its relationship to colony stimulating factor . J. Reticuloendothel. Soc. , 23 , 269 – 285 ( 1978. ). [PubMed] [Google Scholar]
- 11. ) Chen , B. D‐M. , Clark , C. R. and Chou , T‐H.Granulocyte/ macrophage colony‐stimulating factor stimulates monocyte and tissue macrophage proliferation and enhances their responsiveness to macrophage colony‐stimulating factor . Blood , 71 , 997 – 1002 ( 1988. ). [PubMed] [Google Scholar]
- 12. ) Chodakewitz , J. A. , Kupper , T. S. and Coleman , D. L.Keratinocyte‐derived granulocyte/macrophage colony‐stimulating factor induces DNA synthesis of peritoneal macrophages . J. Immunol. , 140 , 832 – 836 ( 1988. ). [PubMed] [Google Scholar]
- 13. ) Old , L. J.Tumor necrosis factor: polypeptide mediator network . Nature , 326 , 330 – 331 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Le , J. and Vilcek , J.Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities . Lab. Invest , 56 , 234 – 238 ( 1987. ). [PubMed] [Google Scholar]
- 15. ) Beutler , B. and Cerami , A.Tumor necrosis, cachexia, shock, and inflammation: a common mediator . Ann. Rev. Biochem. , 57 , 505 – 518 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Old , L. J.Tumor necrosis factor (TNF) . Science , 230 , 630 – 632 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Beutler , B. and Cerami , A.Cachectin and tumor necrosis factor as two sides of the same biological coin . Nature , 320 , 584 – 588 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Satoh , M. , Shimada , Y. , Inagawa , H. , Minagawa , H. , Kajikawa , T. , Oshima , H. , Abe , S. , Yamazaki , M. and Mizuno , D.Priming effect of interferons and interleukin 2 on endogenous production of tumor necrosis factor in mice . Jpn. J. Cancer Res. , 77 , 342 – 344 ( 1986. ). [PubMed] [Google Scholar]
- 19. ) Mosmann , T.Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays . J. Immunol. Methods , 65 , 55 – 63 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Nakagawara , A. and Nathan , C. F.A simple method for counting adherent cells: application to cultured human monocytes, macrophages and multinucleated giant cells . J. Immunol. Methods , 56 , 261 – 268 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Zuckerman , S. H. , Evans , G. F‐ , Snyder , Y. M. and Roeder , W. D.Endotoxin‐macrophage interaction: posttranslational regulation of tumor necrosis factor expression . J. Immunol. , 143 , 1223 – 1227 ( 1989. ). [PubMed] [Google Scholar]
- 22. ) Beutler , B. , Krochin , N. , Milsark , I. W. , Luedke , C. and Cerami , A.Control of cachectin (tumor necrosis factor) synthesis: mechanism of endotoxin resistance . Science , 232 , 977 – 980 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Taramelli , D. and Veresio , L.Activation of murine macrophages. I. Different pattern of activation by poly I:C than by lymphokine or LPS . J. Immunol. , 127 , 58 – 63 ( 1981. ). [PubMed] [Google Scholar]
- 24. ) Scultz , R , M. , Pavlidis , Stylos N. A. W. A. and Chirigos , M. A.Regulation of macrophage tumoricidal function: a role for prostaglandins of the E series . Nature , 202 , 320 – 321 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 25. ) Knudsen , P. J. , Dinarello , C. A. and Strom , T. B.Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate . J. Immunol. , 137 , 3189 – 3194 ( 1986. ). [PubMed] [Google Scholar]
- 26. ) Renz , H. , , G‐H.Gong Schmidt , A. , Nain , M. and Gemsa , D.Release of tumor necrosis factor‐α from macrophages: enhancement and suppression are dose‐dependently regulated by prostaglandin E2 and cyclic nucleotides . J. Immunol. , 141 , 2388 – 2393 ( 1988. ). [PubMed] [Google Scholar]
- 27. ) Luedke , C. E. and Cerami , A.Interferon‐γ overcomes glucocorticoid suppression of cachectin/tumor necrosis factor biosynthesis by murine macrophages . J. Clin, Invest. , 86 , 1234 – 1240 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. ) Dunkam , D. M. , Arkins , S. , Edwards , C. K. , III , Dantzen , R. and Kelly , K. W.Role of interferon‐γ in counteracting the suppressive effects of transforming growth factor‐β 2 and glucocorticoids on the production of tumor necrosis factors . J. Leukocyte Biol. , 48 , 473 – 481 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 29. ) Ding , A. H. and Nathan , C. F.Trace levels of bacterial lipopolysaccharide prevent interferon‐γ or tumor necrosis factor‐a from enhancing mouse peritoneal macrophage respiratory burst capacity . J. Immunol. , 139 , 1971 – 1977 ( 1987. ). [PubMed] [Google Scholar]
- 30. ) Hamilton , T. A. , Guoping , M. A. and Chisolm , G. M.Oxidized low density lipoprotein suppresses the expression of tumor necrosis factor‐α mRNA in stimulated murine peritoneal macrophages . J. Immunol. , 144 , 2343 – 2350 ( 1990. ). [PubMed] [Google Scholar]