Abstract
The abilities of human alveolar macrophages (AM) obtained from healthy donors and patients with lung cancer to produce tumor necrosis factor (TNF) were compared with those of their blood monocytes after activation with lipopolysaccharide (LPS). TNF activity was assayed by measuring cytotoxicity against actinomycin D‐treated L929 cells and TNF was determined quantitatively by sandwich enzyme‐linked immnnosorbent assay (ELISA) with polyclonal and monoclonal antibodies against TNF‐α. Unstimulated AM from healthy donors released variable amounts of TNF spontaneously, whereas blood monocytes did not. When treated with LPS for 24 h, AM and monocytes produced TNF dose‐dependently, but TNF production by AM was significantly more than that by blood monocytes. This TNF activity was inhibited completely by monoclonal anti‐TNF‐α antibody. Macrophages generated by in vitro maturation of monocytes induced by granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) produced more TNF than freshly isolated monocytes. No difference was found in the abilities of AM from healthy donors and patients with lung cancer to produce TNF after activation stimuli. These observations suggest that human AM may be important in in vivo antitumor defense of the lung through TNF‐α production.
Keywords: Macrophage, Tumor necrosis factor‐α, Lung cancer, Monocyte
Full Text
The Full Text of this article is available as a PDF (446.2 KB).
REFERENCES
- 1. ) Fidler , I. J.Macrophages and metastasis — a biological approach to cancer therapy, Presidential Address . Cancer Res. , 45 , 4714 – 4726 ( 1985. ). [PubMed] [Google Scholar]
- 2. ) Sone , S.Role of alveolar macrophages in pulmonary neoplasias . Biochim. Biophys. Acta , 823 , 227 – 245 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Sone , S. , Moriguchi , S. , Shimizu , E. , Ogushi , F. and Tsubura , E.In vitro generation of tumoricidal properties in human alveolar macrophages following interaction with endotoxin . Cancer Res. , 42 , 2227 – 2231 ( 1982. ). [PubMed] [Google Scholar]
- 4. ) Saiki , I.Sone , S. , Fogler , W. E. , Kleinerman , E. S. , Lopez‐Berestein , G. and Fidler , I. J.Synergism between human recombinant γ‐interferon and muramyl dipeptide encapsulated in liposomes for activation of antitumor properties in human blood monocytes . Cancer Res. , 45 , 6188 – 6193 ( 1985. ). [PubMed] [Google Scholar]
- 5. ) Ruco , L. P. and Meltzer , M. S.Macrophage activation for tumor cytotoxicity: development of macrophage cytotoxic activity requires completion of a sequence of short‐lived intermediary reactions . J. Immunol. , 121 , 2035 – 2042 ( 1978. ). [PubMed] [Google Scholar]
- 6. ) Utsugi , T. and Sone , S.Comparative analysis of the priming effect of human interferon‐γ, α and β on synergism with muramyl dipeptide analog for anti‐tumor expression of human blood monocytes . J. Immunol. , 136 , 1117 – 1122 ( 1986. ). [PubMed] [Google Scholar]
- 7. ) Nathan , C. F.Secretory products of macrophages . J. Clin. Invest. , 79 , 319 – 326 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Currie , G. and Basham , C.Differential arginine dependence and the selective cytotoxic effects of activated macrophages for malignant cells in vitro . Br. J. Cancer , 38 , 653 – 659 ( 1978. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. ) Adams , D. O. , Kao , K. , Farb , R. and Pizzo , S. V.Effector mechanism of cytolytically activated macrophages. II Secretion of a cytolytic factor by activated macrophages and its relationship to secreted neutral protease . J. Immunol. , 124 , 294 – 300 ( 1980. ). [PubMed] [Google Scholar]
- 10. ) Onozaki , K. , Matsushima , K. , Aggarawal , B. B. and Oppenheim , J. J.Human interleukin 1 is a cytocidal factor for several tumor cell lines . J. Immunol. , 135 , 3962 – 3967 ( 1985. ). [PubMed] [Google Scholar]
- 11. ) Ziegler‐Heitbrook , H. W. , Moller , A. , Link , R. P. , Hass , J. G. , Rieber , E. P. and Riethmuller , G.Tumor necrosis factor as effector molecule in monocyte‐mediated cytotoxicity . Cancer Res. , 46 , 5947 – 5952 ( 1986. ). [PubMed] [Google Scholar]
- 12. ) Carswell , E. A. , Old , L. J. , Kassel , R. L. , Green , S. , Fiore , N. , and Williamson , B.An endotoxin induced serum factor that causes necrosis of tumors . Proc. Natl. Acad. Sci. USA , 72 , 3666 – 3670 ( 1975. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. ) Munker , M. , Munker , R. , Saxta , R. E. and Koeffer , H. P.Effect of recombinant monokine, lymphokine, and other agents on clonal proliferation of human lung cancer cell lines . Cancer Res. , 47 , 4081 – 4085 ( 1987. ). [PubMed] [Google Scholar]
- 14. ) Beutler , B. and Cerami , A.Cachectin: more than a tumor necrosis factor . N. Eng. J. Med. , 317 , 379 – 385 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Vela , G. P. and Spector , W. G.The origin and turnover of alveolar macrophages in experimental pneumonia . J. Pathol. , 109 , 7 – 19 ( 1973. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Goldstein , E. W. , Lippert , W. and Warshauer , K.Pulmonary alveolar macrophages: defenders against bacterial infection of the lung . J. Clin. Invest. , 54 , 519 – 528 ( 1974. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. ) Sone , S. , Tachibana , K. , Ishii , K. , Ogawara , M. and Tsubura , E.Production of a tumor cytolytic factor(s) by activated human alveolar macrophages and its action . Cancer Res. , 44 , 646 – 651 ( 1984. ). [PubMed] [Google Scholar]
- 18. ) Sone , S. , Mutsuura , S. , Ishii , K. , Shirahama , T. and Tsubura , E.In vitro cytotoxicity to various human tumor cell lines of a tumor cytotoxic factor(S) produced by human alveolar macrophages . Gann , 75 , 920 – 928 ( 1984. ). [PubMed] [Google Scholar]
- 19. ) Tanaka , K. , Ishikawa , E. , Ohmoto , Y. and Hirai , Y.In vitro production of human interleukin 1α and interleukin‐1β by peripheral blood mononuclear cells examined by sensitive sandwich enzyme immunoassay . Eur. J. Immunol. , 17 , 1527 – 1530 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Chen , D. M. , Clark , C. R. and Chou , T.Granulocyte/macrophage colony‐stimulating factor stimulates mono‐cytes and tissue macrophage proliferation and enhances their responsiveness to macrophage colony‐stimulating factor . Blood , 71 , 997 – 1002 ( 1988. ). [PubMed] [Google Scholar]
- 21. ) Lemarbre , P. , Hoidal , J. , Vesella , R. and Rinehart , J.Human pulmonary macrophage tumor cell cytotoxicity , Blood , 55 , 612 – 617 ( 1980. ). [PubMed] [Google Scholar]
- 22. ) Nakahashi , H. , Yasumoto , K. and Nagashima , A.Anti‐tumor activity of macrophages in lung cancer patients with special reference to location of macrophages . Cancer Res. , 44 , 5906 – 5909 ( 1984. ). [PubMed] [Google Scholar]
- 23. ) Kan‐Mitchell , J. , Hengst , J. C. D. , Kempf , R. A. , Rothbart , R. K. , Simons , S. M. , Brooker , A. S. , Kortes , V. L. and Mitchell , M. S.Cytotoxic activity of pulmonary alveolar macrophages . Cancer Res. , 45 , 453 – 458 ( 1985. ). [PubMed] [Google Scholar]
- 24. ) Wewers , M. D. , Rennard , S. I. , Hance , A. J. , Bitterman , P. B. and Crystal , R. G.Normal human alveolar macrophages obtained by bronchoalveolar lavage have a limited capacity to release interleukin‐1 . J. Clin. Invest. , 74 , 2208 – 2218 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. ) Sone , S. , Okubo , A. and Ogura , T.Normal human alveolar macrophages have more ability than blood monocytes to produce cell‐associated interleukin 1 . Am. J. Respir. Cell Mol. Biol. , 1 , 507 – 515 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 26. ) Sone , S. , Lopez‐Berestein , G. and Fidler , I. J.Kinetics and function of tumor cytotoxic factor(s) produced by human blood monocytes activated to the tumoricidal state . J. Natl. Cancer Inst. , 74 , 583 – 590 ( 1985. ). [PubMed] [Google Scholar]
- 27. ) Becker , S. , Devlin , R. B. and Haskill , J. S.Differential production of tumor necrosis factor, macrophage colony stimulating factor, and interleukin 1 by human alveolar macrophages . J. Leukocyte Biol. , 45 , 353 – 361 ( 1989. ). [PubMed] [Google Scholar]
- 28. ) Martinet , Y. , Yamauchi , K. , and Crystal , R. G.Differential expression of tumor necrosis factor/cachectin gene by blood and lung mononuclear phagocytes . Am. Rev. Respir. Dis. , 138 , 659 – 665 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 29. ) Kimura , S. , Sone , S. , Takahashi , K. , Uyama , T. , Ogura , T. and Monden , Y.Antitumor potential of pleural cavity macrophages in lung cancer patients without malignant effusion . Br. J. Cancer , 59 , 535 – 539 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. ) Burchett , S. K. , Weaver , W. M. , Westell , J. A. , Larsen , A. , Kronheim , T. A. and Wilson , C. B.Regulation of tumor necrosis factor/cachectin and IL‐1 secretion in human mononuclear phagocytes . J. Immunol. , 140 , 3473 – 3481 ( 1988. ). [PubMed] [Google Scholar]
- 31. ) Hart , P. H. , Whitty , G. A. , Piccoli , D. S. and Hamilton , J. H.Synergistic activation of human monocytes by granulocyte‐macrophage colony‐stimulating factor and IFN‐γ: increased TNF‐α but not IL‐1 activity . J. Immunol. , 141 , 1516 – 1521 ( 1988. ). [PubMed] [Google Scholar]
- 32. ) Swinburne , S. , Moore , M. and Cole , P.Human bronchoalveolar macrophage cytotoxicity for cultured human lung‐tumour cells . Br. J. Cancer , 46 , 625 – 634 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. ) Thomassen , M. J. , Wiedemann , H. P. , Barna , B. P. , Farmer , M. and Ahmad , M.Induction of in vitro tumoricidal activity in alveolar macrophages and monocytes from patients with lung cancer . Cancer Res. , 48 , 3949 – 3953 ( 1988. ). [PubMed] [Google Scholar]