Abstract
Two cDNAs coding for distinct interleukin 8 (IL-8) receptors, IL-8R1 [Murphy and Tiffany (1991) Science 253, 1280-1283] and IL-8R2 [Holmes, Lee, Kuang, Rice and Wood (1991) Science 253, 1278-1280] have been reported, and biochemical studies on human neutrophils have revealed two proteins (p70 and p44) that bind IL-8 with high affinity [Moser, Schumacher, von Tscharner, Clark-Lewis and Baggiolini (1991), J. Biol. Chem. 266, 10666-10671]. We have cloned the cDNA coding for IL-8R1 from a library of differentiated HL-60 cells. Transfection of this cDNA into Jurkat cells resulted in the expression of high-affinity binding for IL-8 and two related cytokines, GRO alpha and neutrophil-activating peptide 2 (Kd 0.5-1.0 nM). Northern-blot analysis with the IL-8R1 cDNA as probe revealed abundant expression of transcripts of different size in human neutrophils and low-level expression of a single RNA species in HL-60 cells differentiated with dimethyl sulphoxide and retinoic acid. Because of the extensive nucleotide sequence similarity of the cDNAs for IL-8R1 and IL-8R2, the reverse-transcription PCR method was used for analysis of RNA expression in myeloid and lymphoid cells, 19 cell lines established from human primary melanomas or metastases, two melanocyte and one fibroblast cell lines. IL-8R1 mRNA transcripts were expressed at high levels in neutrophils, and to a lesser extent in blood monocytes and the myeloid cell lines, HL-60 and AML 193, but were not found in THP-1 cells, lymphocytes and Jurkat cells. IL-8R2 mRNA transcripts, by contrast, were found in all blood cells and related cell lines, as well as in all melanoma, melanocyte and fibroblast cell lines tested. As for IL-8R1, IL-8R2 mRNA expression was highest in neutrophils. These results suggest that IL-8R1 and IL-8R2 may both be involved in neutrophil activation by IL-8 and related cytokines, and presumably correspond to p70 and p44, the receptors that were identified biochemically. Possible IL-8 functions on lymphocytes and melanoma cells, e.g. chemotaxis and proliferation, must be independent of IL-8R1 and may be mediated by IL-8R2.
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- Anisowicz A., Zajchowski D., Stenman G., Sager R. Functional diversity of gro gene expression in human fibroblasts and mammary epithelial cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9645–9649. doi: 10.1073/pnas.85.24.9645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aruffo A., Seed B. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8573–8577. doi: 10.1073/pnas.84.23.8573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baggiolini M., Clark-Lewis I. Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett. 1992 Jul 27;307(1):97–101. doi: 10.1016/0014-5793(92)80909-z. [DOI] [PubMed] [Google Scholar]
- 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]
- Besemer J., Hujber A., Kuhn B. Specific binding, internalization, and degradation of human neutrophil activating factor by human polymorphonuclear leukocytes. J Biol Chem. 1989 Oct 15;264(29):17409–17415. [PubMed] [Google Scholar]
- Boulay F., Tardif M., Brouchon L., Vignais P. Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA. Biochem Biophys Res Commun. 1990 May 16;168(3):1103–1109. doi: 10.1016/0006-291x(90)91143-g. [DOI] [PubMed] [Google Scholar]
- Boulay F., Tardif M., Brouchon L., Vignais P. The human N-formylpeptide receptor. Characterization of two cDNA isolates and evidence for a new subfamily of G-protein-coupled receptors. Biochemistry. 1990 Dec 18;29(50):11123–11133. doi: 10.1021/bi00502a016. [DOI] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Clark-Lewis I., Moser B., Walz A., Baggiolini M., Scott G. J., Aebersold R. Chemical synthesis, purification, and characterization of two inflammatory proteins, neutrophil activating peptide 1 (interleukin-8) and neutrophil activating peptide. Biochemistry. 1991 Mar 26;30(12):3128–3135. doi: 10.1021/bi00226a021. [DOI] [PubMed] [Google Scholar]
- Colditz I., Zwahlen R., Dewald B., Baggiolini M. In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am J Pathol. 1989 Apr;134(4):755–760. [PMC free article] [PubMed] [Google Scholar]
- Colombo M. P., Maccalli C., Mattei S., Melani C., Radrizzani M., Parmiani G. Expression of cytokine genes, including IL-6, in human malignant melanoma cell lines. Melanoma Res. 1992 Sep;2(3):181–189. doi: 10.1097/00008390-199209000-00006. [DOI] [PubMed] [Google Scholar]
- Dahinden C. A., Kurimoto Y., De Weck A. L., Lindley I., Dewald B., Baggiolini M. The neutrophil-activating peptide NAF/NAP-1 induces histamine and leukotriene release by interleukin 3-primed basophils. J Exp Med. 1989 Nov 1;170(5):1787–1792. doi: 10.1084/jem.170.5.1787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Detmers P. A., Powell D. E., Walz A., Clark-Lewis I., Baggiolini M., Cohn Z. A. Differential effects of neutrophil-activating peptide 1/IL-8 and its homologues on leukocyte adhesion and phagocytosis. J Immunol. 1991 Dec 15;147(12):4211–4217. [PubMed] [Google Scholar]
- Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Grob P. M., David E., Warren T. C., DeLeon R. P., Farina P. R., Homon C. A. Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8. J Biol Chem. 1990 May 15;265(14):8311–8316. [PubMed] [Google Scholar]
- Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holmes W. E., Lee J., Kuang W. J., Rice G. C., Wood W. I. Structure and functional expression of a human interleukin-8 receptor. Science. 1991 Sep 13;253(5025):1278–1280. doi: 10.1126/science.1840701. [DOI] [PubMed] [Google Scholar]
- 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]
- Leonard E. J., Yoshimura T., Tanaka S., Raffeld M. Neutrophil recruitment by intradermally injected neutrophil attractant/activation protein-1. J Invest Dermatol. 1991 May;96(5):690–694. doi: 10.1111/1523-1747.ep12470612. [DOI] [PubMed] [Google Scholar]
- Michel G., Kemény L., Peter R. U., Beetz A., Ried C., Arenberger P., Ruzicka T. Interleukin-8 receptor-mediated chemotaxis of normal human epidermal cells. FEBS Lett. 1992 Jul 6;305(3):241–243. doi: 10.1016/0014-5793(92)80677-9. [DOI] [PubMed] [Google Scholar]
- Moser B., Clark-Lewis I., Zwahlen R., Baggiolini M. Neutrophil-activating properties of the melanoma growth-stimulatory activity. J Exp Med. 1990 May 1;171(5):1797–1802. doi: 10.1084/jem.171.5.1797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moser B., Schumacher C., von Tscharner V., Clark-Lewis I., Baggiolini M. Neutrophil-activating peptide 2 and gro/melanoma growth-stimulatory activity interact with neutrophil-activating peptide 1/interleukin 8 receptors on human neutrophils. J Biol Chem. 1991 Jun 5;266(16):10666–10671. [PubMed] [Google Scholar]
- Murphy P. M., Tiffany H. L. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science. 1991 Sep 13;253(5025):1280–1283. doi: 10.1126/science.1891716. [DOI] [PubMed] [Google Scholar]
- Nakamura M., Honda Z., Izumi T., Sakanaka C., Mutoh H., Minami M., Bito H., Seyama Y., Matsumoto T., Noma M. Molecular cloning and expression of platelet-activating factor receptor from human leukocytes. J Biol Chem. 1991 Oct 25;266(30):20400–20405. [PubMed] [Google Scholar]
- Oppenheim J. J., Zachariae C. O., Mukaida N., Matsushima K. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu Rev Immunol. 1991;9:617–648. doi: 10.1146/annurev.iy.09.040191.003153. [DOI] [PubMed] [Google Scholar]
- 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]
- Radrizzani M., Benedetti B., Castelli C., Longo A., Ferrara G. B., Herlyn M., Parmiani G., Fossati G. Human allogeneic melanoma-reactive T-helper lymphocyte clones: functional analysis of lymphocyte-melanoma interactions. Int J Cancer. 1991 Dec 2;49(6):823–830. doi: 10.1002/ijc.2910490605. [DOI] [PubMed] [Google Scholar]
- Richmond A., Balentien E., Thomas H. G., Flaggs G., Barton D. E., Spiess J., Bordoni R., Francke U., Derynck R. Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin. EMBO J. 1988 Jul;7(7):2025–2033. doi: 10.1002/j.1460-2075.1988.tb03042.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samanta A. K., Oppenheim J. J., Matsushima K. Identification and characterization of specific receptors for monocyte-derived neutrophil chemotactic factor (MDNCF) on human neutrophils. J Exp Med. 1989 Mar 1;169(3):1185–1189. doi: 10.1084/jem.169.3.1185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samanta A. K., Oppenheim J. J., Matsushima K. Interleukin 8 (monocyte-derived neutrophil chemotactic factor) dynamically regulates its own receptor expression on human neutrophils. J Biol Chem. 1990 Jan 5;265(1):183–189. [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schnitzel W., Garbeis B., Monschein U., Besemer J. Neutrophil activating peptide-2 binds with two affinities to receptor(s) on human neutrophils. Biochem Biophys Res Commun. 1991 Oct 15;180(1):301–307. doi: 10.1016/s0006-291x(05)81292-6. [DOI] [PubMed] [Google Scholar]
- Schumacher C., Clark-Lewis I., Baggiolini M., Moser B. High- and low-affinity binding of GRO alpha and neutrophil-activating peptide 2 to interleukin 8 receptors on human neutrophils. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10542–10546. doi: 10.1073/pnas.89.21.10542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swensson O., Schubert C., Christophers E., Schröder J. M. Inflammatory properties of neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8) in human skin: a light- and electronmicroscopic study. J Invest Dermatol. 1991 May;96(5):682–689. doi: 10.1111/1523-1747.ep12470606. [DOI] [PubMed] [Google Scholar]
- Thomas K. M., Taylor L., Navarro J. The interleukin-8 receptor is encoded by a neutrophil-specific cDNA clone, F3R. J Biol Chem. 1991 Aug 15;266(23):14839–14841. [PubMed] [Google Scholar]
- Tokunaga K., Nakamura Y., Sakata K., Fujimori K., Ohkubo M., Sawada K., Sakiyama S. Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers. Cancer Res. 1987 Nov 1;47(21):5616–5619. [PubMed] [Google Scholar]
- Ueda K., Clark D. P., Chen C. J., Roninson I. B., Gottesman M. M., Pastan I. The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation. J Biol Chem. 1987 Jan 15;262(2):505–508. [PubMed] [Google Scholar]
- Walz A., Baggiolini M. Generation of the neutrophil-activating peptide NAP-2 from platelet basic protein or connective tissue-activating peptide III through monocyte proteases. J Exp Med. 1990 Feb 1;171(2):449–454. doi: 10.1084/jem.171.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walz A., Dewald B., von Tscharner V., Baggiolini M. Effects of the neutrophil-activating peptide NAP-2, platelet basic protein, connective tissue-activating peptide III and platelet factor 4 on human neutrophils. J Exp Med. 1989 Nov 1;170(5):1745–1750. doi: 10.1084/jem.170.5.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walz A., Meloni F., Clark-Lewis I., von Tscharner V., Baggiolini M. [Ca2+]i changes and respiratory burst in human neutrophils and monocytes induced by NAP-1/interleukin-8, NAP-2, and gro/MGSA. J Leukoc Biol. 1991 Sep;50(3):279–286. doi: 10.1002/jlb.50.3.279. [DOI] [PubMed] [Google Scholar]
- Walz A., Zwahlen R., Baggiolini M. Formation and biological properties of neutrophil activating peptide 2 (NAP-2). Adv Exp Med Biol. 1991;305:39–46. doi: 10.1007/978-1-4684-6009-4_5. [DOI] [PubMed] [Google Scholar]
- Wang J. M., Taraboletti G., Matsushima K., Van Damme J., Mantovani A. Induction of haptotactic migration of melanoma cells by neutrophil activating protein/interleukin-8. Biochem Biophys Res Commun. 1990 May 31;169(1):165–170. doi: 10.1016/0006-291x(90)91449-3. [DOI] [PubMed] [Google Scholar]