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. 1994 Feb;144(2):393–403.

Induction of interleukin-8 synthesis from monocytes by human C5a anaphylatoxin.

J A Ember 1, S D Sanderson 1, T E Hugli 1, E L Morgan 1
PMCID: PMC1887151  PMID: 7508686

Abstract

Interleukin-8 (IL-8) is an important mediator of inflammation and has been shown to be a potent chemotactic/cell activator for polymorphonuclear neutrophils (PMNs). T lymphocytes, and basophils. Cellular sources of IL-8 include monocytes, PMNs, endothelial cells, epithelial cells, and keratinocytes when stimulated by factors such as lipopolysaccharide, IL-1, and tumor necrosis factor-alpha. This report demonstrates that C5a, in addition to being a direct mediator of inflammation, can induce both IL-8 synthesis and high levels of release from monocytes. Natural human C5a and a synthetic C-terminal analogue peptide of C5a each induced IL-8 synthesis and release from CD14+ human peripheral blood mononuclear cells. Antigenic reactivity based on enzyme-linked immunosorbent assay gave evidence that IL-8 was present in the culture supernatants of stimulated peripheral blood mononuclear cells. Proof that supernatant levels of IL-8 attain biologically significant quantities was provided by human PMN chemotaxis assays. The quantity of IL-8 recovered from C5a-activated monocytes in peripheral blood mononuclear cells is up to 1,000-fold greater than that released from comparable numbers of PMNs under similar conditions. Therefore, IL-8 released from C5a-activated monocytes may play a significant role in expanding and prolonging cellular infiltration and activation at sites of infection, inflammation, or tissue injury. This observation suggests an important humoral amplification loop for inflammatory events involving both complement activation and cytokine release.

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Selected References

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

  1. Baggiolini M., Walz A., Kunkel S. L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J Clin Invest. 1989 Oct;84(4):1045–1049. doi: 10.1172/JCI114265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barker J. N., Jones M. L., Mitra R. S., Crockett-Torabe E., Fantone J. C., Kunkel S. L., Warren J. S., Dixit V. M., Nickoloff B. J. Modulation of keratinocyte-derived interleukin-8 which is chemotactic for neutrophils and T lymphocytes. Am J Pathol. 1991 Oct;139(4):869–876. [PMC free article] [PubMed] [Google Scholar]
  3. Boulay F., Mery L., Tardif M., Brouchon L., Vignais P. Expression cloning of a receptor for C5a anaphylatoxin on differentiated HL-60 cells. Biochemistry. 1991 Mar 26;30(12):2993–2999. doi: 10.1021/bi00226a002. [DOI] [PubMed] [Google Scholar]
  4. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  5. Cassatella M. A., Bazzoni F., Ceska M., Ferro I., Baggiolini M., Berton G. IL-8 production by human polymorphonuclear leukocytes. The chemoattractant formyl-methionyl-leucyl-phenylalanine induces the gene expression and release of IL-8 through a pertussis toxin-sensitive pathway. J Immunol. 1992 May 15;148(10):3216–3220. [PubMed] [Google Scholar]
  6. Cerami A. Inflammatory cytokines. Clin Immunol Immunopathol. 1992 Jan;62(1 Pt 2):S3–10. doi: 10.1016/0090-1229(92)90035-m. [DOI] [PubMed] [Google Scholar]
  7. Cochrane C. G., Müller-Eberhard H. J. The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med. 1968 Feb 1;127(2):371–386. doi: 10.1084/jem.127.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DeForge L. E., Remick D. G. Kinetics of TNF, IL-6, and IL-8 gene expression in LPS-stimulated human whole blood. Biochem Biophys Res Commun. 1991 Jan 15;174(1):18–24. doi: 10.1016/0006-291x(91)90478-p. [DOI] [PubMed] [Google Scholar]
  9. DeForge L. E., Tracey D. E., Kenney J. S., Remick D. G. Interleukin-1 receptor antagonist protein inhibits interleukin-8 expression in lipopolysaccharide-stimulated human whole blood. Am J Pathol. 1992 May;140(5):1045–1054. [PMC free article] [PubMed] [Google Scholar]
  10. Dohlman H. G., Thorner J., Caron M. G., Lefkowitz R. J. Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem. 1991;60:653–688. doi: 10.1146/annurev.bi.60.070191.003253. [DOI] [PubMed] [Google Scholar]
  11. Ember J. A., Sanderson S. D., Taylor S. M., Kawahara M., Hugli T. E. Biologic activity of synthetic analogues of C5a anaphylatoxin. J Immunol. 1992 May 15;148(10):3165–3173. [PubMed] [Google Scholar]
  12. Fernandez H. N., Henson P. M., Otani A., Hugli T. E. Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions. J Immunol. 1978 Jan;120(1):109–115. [PubMed] [Google Scholar]
  13. Fukuoka Y., Hugli T. E. Anaphylatoxin binding and degradation by rat peritoneal mast cells. Mechanisms of degranulation and control. J Immunol. 1990 Sep 15;145(6):1851–1858. [PubMed] [Google Scholar]
  14. Gerard N. P., Gerard C. The chemotactic receptor for human C5a anaphylatoxin. Nature. 1991 Feb 14;349(6310):614–617. doi: 10.1038/349614a0. [DOI] [PubMed] [Google Scholar]
  15. Goldstein I. M., Weissmann G. Generation of C5-derived lysosomal enzyme-releasing activity (C5a) by lysates of leukocyte lysosomes. J Immunol. 1974 Nov;113(5):1583–1588. [PubMed] [Google Scholar]
  16. Goodman M. G., Chenoweth D. E., Weigle W. O. Induction of interleukin 1 secretion and enhancement of humoral immunity by binding of human C5a to macrophage surface C5a receptors. J Exp Med. 1982 Sep 1;156(3):912–917. doi: 10.1084/jem.156.3.912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goodman M. G., Chenoweth D. E., Weigle W. O. Potentiation of the primary humoral immune response in vitro by C5a anaphylatoxin. J Immunol. 1982 Jul;129(1):70–75. [PubMed] [Google Scholar]
  18. Hechtman D. H., Cybulsky M. I., Fuchs H. J., Baker J. B., Gimbrone M. A., Jr Intravascular IL-8. Inhibitor of polymorphonuclear leukocyte accumulation at sites of acute inflammation. J Immunol. 1991 Aug 1;147(3):883–892. [PubMed] [Google Scholar]
  19. Huey R., Hugli T. E. Characterization of a C5a receptor on human polymorphonuclear leukocytes (PMN). J Immunol. 1985 Sep;135(3):2063–2068. [PubMed] [Google Scholar]
  20. Hugli T. E. Structure and function of the anaphylatoxins. Springer Semin Immunopathol. 1984;7(2-3):193–219. doi: 10.1007/BF01893020. [DOI] [PubMed] [Google Scholar]
  21. Johnson A. R., Hugli T. E., Müller-Eberhard H. J. Release of histamine from rat mast cells by the complement peptides C3a and C5a. Immunology. 1975 Jun;28(6):1067–1080. [PMC free article] [PubMed] [Google Scholar]
  22. Johnson R. J., Chenoweth D. E. Labeling the granulocyte C5a receptor with a unique photoreactive probe. J Biol Chem. 1985 Jun 25;260(12):7161–7164. [PubMed] [Google Scholar]
  23. Kristensen M. S., Paludan K., Larsen C. G., Zachariae C. O., Deleuran B. W., Jensen P. K., Jørgensen P., Thestrup-Pedersen K. Quantitative determination of IL-1 alpha-induced IL-8 mRNA levels in cultured human keratinocytes, dermal fibroblasts, endothelial cells, and monocytes. J Invest Dermatol. 1991 Sep;97(3):506–510. doi: 10.1111/1523-1747.ep12481543. [DOI] [PubMed] [Google Scholar]
  24. Larsen C. G., Anderson A. O., Appella E., Oppenheim J. J., Matsushima K. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science. 1989 Mar 17;243(4897):1464–1466. doi: 10.1126/science.2648569. [DOI] [PubMed] [Google Scholar]
  25. Madsen M., Johnsen H. E. A methodological study of E-rosette formation using AET-treated sheep red blood cells. J Immunol Methods. 1979 May 10;27(1):61–74. doi: 10.1016/0022-1759(79)90239-4. [DOI] [PubMed] [Google Scholar]
  26. Matsushima K., Morishita K., Yoshimura T., Lavu S., Kobayashi Y., Lew W., Appella E., Kung H. F., Leonard E. J., Oppenheim J. J. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med. 1988 Jun 1;167(6):1883–1893. doi: 10.1084/jem.167.6.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Matsushima K., Morishita K., Yoshimura T., Lavu S., Kobayashi Y., Lew W., Appella E., Kung H. F., Leonard E. J., Oppenheim J. J. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med. 1988 Jun 1;167(6):1883–1893. doi: 10.1084/jem.167.6.1883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Matsushima K., Oppenheim J. J. Interleukin 8 and MCAF: novel inflammatory cytokines inducible by IL 1 and TNF. Cytokine. 1989 Nov;1(1):2–13. doi: 10.1016/1043-4666(89)91043-0. [DOI] [PubMed] [Google Scholar]
  29. Morgan E. L., Ember J. A., Sanderson S. D., Scholz W., Buchner R., Ye R. D., Hugli T. E. Anti-C5a receptor antibodies. Characterization of neutralizing antibodies specific for a peptide, C5aR-(9-29), derived from the predicted amino-terminal sequence of the human C5a receptor. J Immunol. 1993 Jul 1;151(1):377–388. [PubMed] [Google Scholar]
  30. Morgan E. L., Sanderson S., Scholz W., Noonan D. J., Weigle W. O., Hugli T. E. Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis. J Immunol. 1992 Jun 15;148(12):3937–3942. [PubMed] [Google Scholar]
  31. Nakamura H., Yoshimura K., Jaffe H. A., Crystal R. G. Interleukin-8 gene expression in human bronchial epithelial cells. J Biol Chem. 1991 Oct 15;266(29):19611–19617. [PubMed] [Google Scholar]
  32. Okusawa S., Dinarello C. A., Yancey K. B., Endres S., Lawley T. J., Frank M. M., Burke J. F., Gelfand J. A. C5a induction of human interleukin 1. Synergistic effect with endotoxin or interferon-gamma. J Immunol. 1987 Oct 15;139(8):2635–2640. [PubMed] [Google Scholar]
  33. Okusawa S., Yancey K. B., van der Meer J. W., Endres S., Lonnemann G., Hefter K., Frank M. M., Burke J. F., Dinarello C. A., Gelfand J. A. C5a stimulates secretion of tumor necrosis factor from human mononuclear cells in vitro. Comparison with secretion of interleukin 1 beta and interleukin 1 alpha. J Exp Med. 1988 Jul 1;168(1):443–448. doi: 10.1084/jem.168.1.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Or Y. S., Clark R. F., Lane B., Mollison K. W., Carter G. W., Luly J. R. Improvements in the minimum binding sequence of C5a: examination of His-67. J Med Chem. 1992 Jan 24;35(2):402–406. doi: 10.1021/jm00080a030. [DOI] [PubMed] [Google Scholar]
  35. Peveri P., Walz A., Dewald B., Baggiolini M. A novel neutrophil-activating factor produced by human mononuclear phagocytes. J Exp Med. 1988 May 1;167(5):1547–1559. doi: 10.1084/jem.167.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rollins T. E., Springer M. S. Identification of the polymorphonuclear leukocyte C5a receptor. J Biol Chem. 1985 Jun 25;260(12):7157–7160. [PubMed] [Google Scholar]
  37. Schindler R., Gelfand J. A., Dinarello C. A. Recombinant C5a stimulates transcription rather than translation of interleukin-1 (IL-1) and tumor necrosis factor: translational signal provided by lipopolysaccharide or IL-1 itself. Blood. 1990 Oct 15;76(8):1631–1638. [PubMed] [Google Scholar]
  38. Scholz W., McClurg M. R., Cardenas G. J., Smith M., Noonan D. J., Hugli T. E., Morgan E. L. C5a-mediated release of interleukin 6 by human monocytes. Clin Immunol Immunopathol. 1990 Nov;57(2):297–307. doi: 10.1016/0090-1229(90)90043-p. [DOI] [PubMed] [Google Scholar]
  39. Sporn S. A., Eierman D. F., Johnson C. E., Morris J., Martin G., Ladner M., Haskill S. Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair. J Immunol. 1990 Jun 1;144(11):4434–4441. [PubMed] [Google Scholar]
  40. Strieter R. M., Kasahara K., Allen R. M., Standiford T. J., Rolfe M. W., Becker F. S., Chensue S. W., Kunkel S. L. Cytokine-induced neutrophil-derived interleukin-8. Am J Pathol. 1992 Aug;141(2):397–407. [PMC free article] [PubMed] [Google Scholar]
  41. Strieter R. M., Kunkel S. L., Showell H. J., Remick D. G., Phan S. H., Ward P. A., Marks R. M. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science. 1989 Mar 17;243(4897):1467–1469. doi: 10.1126/science.2648570. [DOI] [PubMed] [Google Scholar]
  42. Suter S. Imbalance between polymorphonuclear leukocyte proteases and antiproteases in chronic pyogenic infections and its relation to the proteolysis of complement component C3. Complement. 1986;3(1):1–24. doi: 10.1159/000467874. [DOI] [PubMed] [Google Scholar]
  43. Thiele D. L., Kurosaka M., Lipsky P. E. Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester. J Immunol. 1983 Nov;131(5):2282–2290. [PubMed] [Google Scholar]
  44. van Epps D. E., Chenoweth D. E. Analysis of the binding of fluorescent C5a and C3a to human peripheral blood leukocytes. J Immunol. 1984 Jun;132(6):2862–2867. [PubMed] [Google Scholar]

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