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. 1988 Apr 1;167(4):1364–1376. doi: 10.1084/jem.167.4.1364

A novel, NH2-terminal sequence-characterized human monokine possessing neutrophil chemotactic, skin-reactive, and granulocytosis-promoting activity

PMCID: PMC2188912  PMID: 3258625

Abstract

A factor able to induce an early local inflammation in rabbit skin was detected in the supernatant of mitogen-stimulated human blood leukocytes. The factor was different from IL-1 which, although present in the supernatants, was chemically separable from the factor and induced a late rather than an early skin response. Other biological effects of the principal factor were its in vitro chemotactic effects on granulocytes and its ability to induce rapid granulocytosis upon intravenous injection in rabbits. When tested under the same conditions, IL-1 beta did not act chemotactically and induced granulocytosis at a later time. The factor was purified to homogeneity and identified by electrophoretic mobility as a protein of Mr 6,500. Amino acid sequence analysis revealed the presence of an uncontaminated NH2-terminal sequence identical to a segment of the sequence previously predicted from the cDNA clone (3-10C) copied from an mRNA isolated from human leukocytes and coding for a protein of unknown function. The NH2- terminal sequence of the factor also showed extensive homology to that of the platelet factors beta-thromboglobulin (beta TG) and platelet factor 4 (PF-4). Studies done to identify the cell source of the factor revealed that it was produced by adherent mononuclear cells but not by platelets, while the opposite was true for beta TG.

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Selected References

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  1. Begg G. S., Pepper D. S., Chesterman C. N., Morgan F. J. Complete covalent structure of human beta-thromboglobulin. Biochemistry. 1978 May 2;17(9):1739–1744. doi: 10.1021/bi00602a024. [DOI] [PubMed] [Google Scholar]
  2. Bloom B. R. In vitro approaches to the mechanism of cell-mediated immune reactions. Adv Immunol. 1971;13:101–208. doi: 10.1016/s0065-2776(08)60184-4. [DOI] [PubMed] [Google Scholar]
  3. Brindley L. L., Sweet J. M., Goetzl E. J. Stimulation of histamine release from human basophils by human platelet factor 4. J Clin Invest. 1983 Oct;72(4):1218–1223. doi: 10.1172/JCI111077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Colditz I. G., Movat H. Z. Kinetics of neutrophil accumulation in acute inflammatory lesions induced by chemotaxins and chemotaxinigens. J Immunol. 1984 Oct;133(4):2169–2173. [PubMed] [Google Scholar]
  5. Deuel T. F., Keim P. S., Farmer M., Heinrikson R. L. Amino acid sequence of human platelet factor 4. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2256–2258. doi: 10.1073/pnas.74.6.2256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Deuel T. F., Senior R. M., Chang D., Griffin G. L., Heinrikson R. L., Kaiser E. T. Platelet factor 4 is chemotactic for neutrophils and monocytes. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4584–4587. doi: 10.1073/pnas.78.7.4584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dinarello C. A. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. doi: 10.1093/clinids/6.1.51. [DOI] [PubMed] [Google Scholar]
  8. Fibbe W. E., van Damme J., Billiau A., Voogt P. J., Duinkerken N., Kluck P. M., Falkenburg J. H. Interleukin-1 (22-K factor) induces release of granulocyte-macrophage colony-stimulating activity from human mononuclear phagocytes. Blood. 1986 Dec;68(6):1316–1321. [PubMed] [Google Scholar]
  9. Gallin J. I., Kirkpatrick C. H. Chemotactic activity in dialyzable transfer factor. Proc Natl Acad Sci U S A. 1974 Feb;71(2):498–502. doi: 10.1073/pnas.71.2.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Georgilis K., Schaefer C., Dinarello C. A., Klempner M. S. Human recombinant interleukin 1 beta has no effect on intracellular calcium or on functional responses of human neutrophils. J Immunol. 1987 May 15;138(10):3403–3407. [PubMed] [Google Scholar]
  12. Hunkapiller M. W., Hood L. E. Analysis of phenylthiohydantoins by ultrasensitive gradient high-performance liquid chromatography. Methods Enzymol. 1983;91:486–493. doi: 10.1016/s0076-6879(83)91045-5. [DOI] [PubMed] [Google Scholar]
  13. Kaplan G., Luster A. D., Hancock G., Cohn Z. A. The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin. J Exp Med. 1987 Oct 1;166(4):1098–1108. doi: 10.1084/jem.166.4.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Katz I. R., Thorbecke G. J., Bell M. K., Yin J. Z., Clarke D., Zucker M. B. Protease-induced immunoregulatory activity of platelet factor 4. Proc Natl Acad Sci U S A. 1986 May;83(10):3491–3495. doi: 10.1073/pnas.83.10.3491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Lane D. A., Pejler G., Flynn A. M., Thompson E. A., Lindahl U. Neutralization of heparin-related saccharides by histidine-rich glycoprotein and platelet factor 4. J Biol Chem. 1986 Mar 25;261(9):3980–3986. [PubMed] [Google Scholar]
  17. Lonky S. A., Wohl H. Stimulation of human leukocyte elastase by platelet factor 4. Physiologic, morphologic, and biochemical effects on hamster lungs in vitro. J Clin Invest. 1981 Mar;67(3):817–826. doi: 10.1172/JCI110099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Luster A. D., Ravetch J. V. Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med. 1987 Oct 1;166(4):1084–1097. doi: 10.1084/jem.166.4.1084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Luster A. D., Unkeless J. C., Ravetch J. V. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985 Jun 20;315(6021):672–676. doi: 10.1038/315672a0. [DOI] [PubMed] [Google Scholar]
  20. Merrill W. W., Naegel G. P., Matthay R. A., Reynolds H. Y. Alveolar macrophage-derived chemotactic factor: kinetics of in vitro production and partial characterization. J Clin Invest. 1980 Feb;65(2):268–276. doi: 10.1172/JCI109668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Sauder D. N., Mounessa N. L., Katz S. I., Dinarello C. A., Gallin J. I. Chemotactic cytokines: the role of leukocytic pyrogen and epidermal cell thymocyte-activating factor in neutrophil chemotaxis. J Immunol. 1984 Feb;132(2):828–832. [PubMed] [Google Scholar]
  23. Schmid J., Weissmann C. Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogen-stimulated human leukocytes. J Immunol. 1987 Jul 1;139(1):250–256. [PubMed] [Google Scholar]
  24. Tono-Oka T., Nakayama M., Matsumoto S. Human monocyte-derived chemotactic factor for granulocytes. Immunology. 1980 Apr;39(4):607–613. [PMC free article] [PubMed] [Google Scholar]
  25. Van Damme J., De Ley M., Claeys H., Billiau A., Vermylen C., De Somer P. Interferon induced in human leukocytes by concanavalin A: isolation and characterization of gamma- and beta-type components. Eur J Immunol. 1981 Nov;11(11):937–942. doi: 10.1002/eji.1830111116. [DOI] [PubMed] [Google Scholar]
  26. Van Damme J., De Ley M., Opdenakker G., Billiau A., De Somer P., Van Beeumen J. Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1. Nature. 1985 Mar 21;314(6008):266–268. doi: 10.1038/314266a0. [DOI] [PubMed] [Google Scholar]
  27. Van Damme J., De Ley M., Van Snick J., Dinarello C. A., Billiau A. The role of interferon-beta 1 and the 26-kDa protein (interferon-beta 2) as mediators of the antiviral effect of interleukin 1 and tumor necrosis factor. J Immunol. 1987 Sep 15;139(6):1867–1872. [PubMed] [Google Scholar]
  28. Van Damme J., Opdenakker G., Simpson R. J., Rubira M. R., Cayphas S., Vink A., Billiau A., Van Snick J. Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J Exp Med. 1987 Mar 1;165(3):914–919. doi: 10.1084/jem.165.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yoshimura T., Matsushima K., Oppenheim J. J., Leonard E. J. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J Immunol. 1987 Aug 1;139(3):788–793. [PubMed] [Google Scholar]
  30. van Damme J., Opdenakker G., de Ley M., Heremans H., Billiau A. Pyrogenic and haematological effects of the interferon-inducing 22K factor (interleukin 1 beta) from human leukocytes. Clin Exp Immunol. 1986 Nov;66(2):303–311. [PMC free article] [PubMed] [Google Scholar]

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