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J Exp Med. 1996 November 1; 184(5): 1939–1951.
PMCID: PMC2192876

Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation

Abstract

We have cloned a novel mouse CC chemokine cDNA from the lung during an allergic inflammatory reaction. The protein encoded by this cDNA is chemotactic for eosinophils, monocytes, and lymphocytes in vitro and in vivo. Based on its similarities in sequence and function with other CC chemokines, we have named it mouse monocyte chemotactic protein-5 (mMCP- 5). Under noninflammatory conditions, expression of mMCP-5 in the lymph nodes and thymus is constitutive and is generally restricted to stromal cells. Neutralization of mMCP-5 protein with specific antibodies during an allergic inflammatory reaction in vivo resulted in a reduction in the number of eosinophils that accumulated in the lung. Moreover, mMCP- 5 mRNA expression in vivo is regulated differently from that of other major CC chemokines in the lung during the allergic reaction, including Eotaxin. The presence of lymphocytes is essential for expression of mMCP-5 by alveolar macrophages and smooth muscle cells in the lung, and the induction of mMCP-5 RNA occurs earlier than that of the eosinophil chemokine Eotaxin during allergic inflammation. In contrast to Eotaxin, mRNA for mMCP-5 can be produced by mast cells. From these results, we postulate that mMCP-5 plays a pivotal role during the early stages of allergic lung inflammation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Gleich GJ. The eosinophil and bronchial asthma: current understanding. J Allergy Clin Immunol. 1990 Feb;85(2):422–436. [PubMed]
  • Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992 Jan 30;326(5):298–304. [PubMed]
  • Sanderson CJ. Interleukin-5, eosinophils, and disease. Blood. 1992 Jun 15;79(12):3101–3109. [PubMed]
  • Schall TJ, Bacon KB. Chemokines, leukocyte trafficking, and inflammation. Curr Opin Immunol. 1994 Dec;6(6):865–873. [PubMed]
  • Broaddus VC, Boylan AM, Hoeffel JM, Kim KJ, Sadick M, Chuntharapai A, Hébert CA. Neutralization of IL-8 inhibits neutrophil influx in a rabbit model of endotoxin-induced pleurisy. J Immunol. 1994 Mar 15;152(6):2960–2967. [PubMed]
  • Sekido N, Mukaida N, Harada A, Nakanishi I, Watanabe Y, Matsushima K. Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature. 1993 Oct 14;365(6447):654–657. [PubMed]
  • Lukacs NW, Strieter RM, Shaklee CL, Chensue SW, Kunkel SL. Macrophage inflammatory protein-1 alpha influences eosinophil recruitment in antigen-specific airway inflammation. Eur J Immunol. 1995 Jan;25(1):245–251. [PubMed]
  • Ganzalo JA, Jia GQ, Aguirre V, Friend D, Coyle AJ, Jenkins NA, Lin GS, Katz H, Lichtman A, Copeland N, et al. Mouse Eotaxin expression parallels eosinophil accumulation during lung allergic inflammation but it is not restricted to a Th2-type response. Immunity. 1996 Jan;4(1):1–14. [PubMed]
  • Jose PJ, Griffiths-Johnson DA, Collins PD, Walsh DT, Moqbel R, Totty NF, Truong O, Hsuan JJ, Williams TJ. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med. 1994 Mar 1;179(3):881–887. [PMC free article] [PubMed]
  • Lukacs NW, Strieter RM, Chensue SW, Kunkel SL. Activation and regulation of chemokines in allergic airway inflammation. J Leukoc Biol. 1996 Jan;59(1):13–17. [PubMed]
  • Wang B, Biron C, She J, Higgins K, Sunshine MJ, Lacy E, Lonberg N, Terhorst C. A block in both early T lymphocyte and natural killer cell development in transgenic mice with high-copy numbers of the human CD3E gene. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9402–9406. [PubMed]
  • Wuyts A, Proost P, Put W, Lenaerts JP, Paemen L, van Damme J. Leukocyte recruitment by monocyte chemotactic proteins (MCPs) secreted by human phagocytes. J Immunol Methods. 1994 Sep 14;174(1-2):237–247. [PubMed]
  • Luo Y, Laning J, Devi S, Mak J, Schall TJ, Dorf ME. Biologic activities of the murine beta-chemokine TCA3. J Immunol. 1994 Nov 15;153(10):4616–4624. [PubMed]
  • Lin G, Finger E, Gutierrez-Ramos JC. Expression of CD34 in endothelial cells, hematopoietic progenitors and nervous cells in fetal and adult mouse tissues. Eur J Immunol. 1995 Jun;25(6):1508–1516. [PubMed]
  • Heeger P, Wolf G, Meyers C, Sun MJ, O'Farrell SC, Krensky AM, Neilson EG. Isolation and characterization of cDNA from renal tubular epithelium encoding murine Rantes. Kidney Int. 1992 Jan;41(1):220–225. [PubMed]
  • Widmer U, Yang Z, van Deventer S, Manogue KR, Sherry B, Cerami A. Genomic structure of murine macrophage inflammatory protein-1 alpha and conservation of potential regulatory sequences with a human homolog, LD78. J Immunol. 1991 Jun 1;146(11):4031–4040. [PubMed]
  • Gordon JR, Galli SJ. Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Nature. 1990 Jul 19;346(6281):274–276. [PubMed]
  • Copeland NG, Jenkins NA. Development and applications of a molecular genetic linkage map of the mouse genome. Trends Genet. 1991 Apr;7(4):113–118. [PubMed]
  • Tominaga A, Takaki S, Koyama N, Katoh S, Matsumoto R, Migita M, Hitoshi Y, Hosoya Y, Yamauchi S, Kanai Y, et al. Transgenic mice expressing a B cell growth and differentiation factor gene (interleukin 5) develop eosinophilia and autoantibody production. J Exp Med. 1991 Feb 1;173(2):429–437. [PMC free article] [PubMed]
  • Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992 Mar 6;68(5):869–877. [PubMed]
  • Rahemtulla A, Fung-Leung WP, Schilham MW, Kündig TM, Sambhara SR, Narendran A, Arabian A, Wakeham A, Paige CJ, Zinkernagel RM, et al. Normal development and function of CD8+ cells but markedly decreased helper cell activity in mice lacking CD4. Nature. 1991 Sep 12;353(6340):180–184. [PubMed]
  • Fung-Leung WP, Schilham MW, Rahemtulla A, Kündig TM, Vollenweider M, Potter J, van Ewijk W, Mak TW. CD8 is needed for development of cytotoxic T cells but not helper T cells. Cell. 1991 May 3;65(3):443–449. [PubMed]
  • Proost P, Wuyts A, Van Damme J. Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1. J Leukoc Biol. 1996 Jan;59(1):67–74. [PubMed]
  • Clark-Lewis I, Kim KS, Rajarathnam K, Gong JH, Dewald B, Moser B, Baggiolini M, Sykes BD. Structure-activity relationships of chemokines. J Leukoc Biol. 1995 May;57(5):703–711. [PubMed]
  • Zhang YJ, Rutledge BJ, Rollins BJ. Structure/activity analysis of human monocyte chemoattractant protein-1 (MCP-1) by mutagenesis. Identification of a mutated protein that inhibits MCP-1-mediated monocyte chemotaxis. J Biol Chem. 1994 Jun 3;269(22):15918–15924. [PubMed]
  • Taub DD, Oppenheim JJ. Chemokines, inflammation and the immune system. Ther Immunol. 1994 Aug;1(4):229–246. [PubMed]
  • Schall TJ, Bacon K, Camp RD, Kaspari JW, Goeddel DV. Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes. J Exp Med. 1993 Jun 1;177(6):1821–1826. [PMC free article] [PubMed]
  • Butcher EC, Picker LJ. Lymphocyte homing and homeostasis. Science. 1996 Apr 5;272(5258):60–66. [PubMed]
  • Girard JP, Springer TA. High endothelial venules (HEVs): specialized endothelium for lymphocyte migration. Immunol Today. 1995 Sep;16(9):449–457. [PubMed]
  • Standiford TJ, Rolfe MW, Kunkel SL, Lynch JP, 3rd, Burdick MD, Gilbert AR, Orringer MB, Whyte RI, Strieter RM. Macrophage inflammatory protein-1 alpha expression in interstitial lung disease. J Immunol. 1993 Sep 1;151(5):2852–2863. [PubMed]
  • Li YS, Shyy YJ, Wright JG, Valente AJ, Cornhill JF, Kolattukudy PE. The expression of monocyte chemotactic protein (MCP-1) in human vascular endothelium in vitro and in vivo. Mol Cell Biochem. 1993 Sep 8;126(1):61–68. [PubMed]
  • Van Damme J, Proost P, Lenaerts JP, Opdenakker G. Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. J Exp Med. 1992 Jul 1;176(1):59–65. [PMC free article] [PubMed]
  • Minty A, Chalon P, Guillemot JC, Kaghad M, Liauzun P, Magazin M, Miloux B, Minty C, Ramond P, Vita N, et al. Molecular cloning of the MCP-3 chemokine gene and regulation of its expression. Eur Cytokine Netw. 1993 Mar-Apr;4(2):99–110. [PubMed]
  • Uguccioni M, Loetscher P, Forssmann U, Dewald B, Li H, Lima SH, Li Y, Kreider B, Garotta G, Thelen M, et al. Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional analogue of MCP-3 and eotaxin. J Exp Med. 1996 May 1;183(5):2379–2384. [PMC free article] [PubMed]
  • Rollins BJ, Morrison ED, Stiles CD. Cloning and expression of JE, a gene inducible by platelet-derived growth factor and whose product has cytokine-like properties. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3738–3742. [PubMed]

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