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Published in: Respiratory Research 1/2009

Open Access 01-12-2009 | Research

Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis

Authors: Yurika Yogo, Seitaro Fujishima, Takashi Inoue, Fumitake Saito, Takayuki Shiomi, Kazuhiro Yamaguchi, Akitoshi Ishizaka

Published in: Respiratory Research | Issue 1/2009

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Abstract

Background

Idiopathic pulmonary fibrosis (IPF) is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiation pneumonitis/pulmonary fibrosis and preliminarily observed an increase in bronchoalveolar (BAL) fluid CCL22 levels of IPF patients.

Methods

We examined the expression of CCR4, a specific receptor for CCL22 and CCL17, in bronchoalveolar lavage (BAL) fluid cells, as well as the levels of CCL22 and CCL17, to elucidate their pathophysiological roles in pulmonary fibrosis. We also studied their immunohistochemical localization.

Results

BAL fluid CCL22 and CCL17 levels were significantly higher in patients with IPF than those with collagen vascular diseases and healthy volunteers, and there was a significant correlation between the levels of CCL22 and CCL17 in patients with IPF. CCL22 levels in the BAL fluid did not correlate with the total cell numbers, alveolar lymphocytes, or macrophages in BAL fluid. However, the CCL22 levels significantly correlated with the numbers of CCR4-expressing alveolar macrophages. By immunohistochemical and immunofluorescence analysis, localization of CCL22 and CCR4 to CD68-positive alveolar macrophages as well as that of CCL17 to hyperplastic epithelial cells were shown. Clinically, CCL22 BAL fluid levels inversely correlated with DLco/VA values in IPF patients.

Conclusion

We speculated that locally overexpressed CCL22 may induce lung dysfunction through recruitment and activation of CCR4-positive alveolar macrophages.
Literature
1.
go back to reference American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001 Am J Respir Crit Care Med 2002,165(2):277–304. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001 Am J Respir Crit Care Med 2002,165(2):277–304.
2.
3.
go back to reference American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS) Am J Respir Crit Care Med 2000,161(2 Pt 1):646–664. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS) Am J Respir Crit Care Med 2000,161(2 Pt 1):646–664.
4.
go back to reference Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, Taguchi Y, Nagai S, Itoh H, Ohi M, et al.: Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2005,171(9):1040–1047.CrossRefPubMed Azuma A, Nukiwa T, Tsuboi E, Suga M, Abe S, Nakata K, Taguchi Y, Nagai S, Itoh H, Ohi M, et al.: Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2005,171(9):1040–1047.CrossRefPubMed
5.
go back to reference Imai T, Chantry D, Raport CJ, Wood CL, Nishimura M, Godiska R, Yoshie O, Gray PW: Macrophage-derived chemokine is a functional ligand for the CC chemokine receptor 4. J Biol Chem 1998,273(3):1764–1768.CrossRefPubMed Imai T, Chantry D, Raport CJ, Wood CL, Nishimura M, Godiska R, Yoshie O, Gray PW: Macrophage-derived chemokine is a functional ligand for the CC chemokine receptor 4. J Biol Chem 1998,273(3):1764–1768.CrossRefPubMed
6.
go back to reference Imai T, Baba M, Nishimura M, Kakizaki M, Takagi S, Yoshie O: The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4. J Biol Chem 1997,272(23):15036–15042.CrossRefPubMed Imai T, Baba M, Nishimura M, Kakizaki M, Takagi S, Yoshie O: The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4. J Biol Chem 1997,272(23):15036–15042.CrossRefPubMed
7.
go back to reference Katoh S, Fukushima K, Matsumoto N, Matsumoto K, Abe K, Onai N, Matsushima K, Matsukura S: Accumulation of CCR4-expressing CD4+ T cells and high concentration of its ligands (TARC and MDC) in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia. Allergy 2003,58(6):518–523.CrossRefPubMed Katoh S, Fukushima K, Matsumoto N, Matsumoto K, Abe K, Onai N, Matsushima K, Matsukura S: Accumulation of CCR4-expressing CD4+ T cells and high concentration of its ligands (TARC and MDC) in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia. Allergy 2003,58(6):518–523.CrossRefPubMed
8.
go back to reference Romagnani S: Cytokines and chemoattractants in allergic inflammation. Mol Immunol 2002,38(12–13):881–885.CrossRefPubMed Romagnani S: Cytokines and chemoattractants in allergic inflammation. Mol Immunol 2002,38(12–13):881–885.CrossRefPubMed
9.
go back to reference Belperio JA, Dy M, Murray L, Burdick MD, Xue YY, Strieter RM, Keane MP: The role of the Th2 CC chemokine ligand CCL17 in pulmonary fibrosis. J Immunol 2004,173(7):4692–4698.CrossRefPubMed Belperio JA, Dy M, Murray L, Burdick MD, Xue YY, Strieter RM, Keane MP: The role of the Th2 CC chemokine ligand CCL17 in pulmonary fibrosis. J Immunol 2004,173(7):4692–4698.CrossRefPubMed
10.
go back to reference Pignatti P, Brunetti G, Moretto D, Yacoub MR, Fiori M, Balbi B, Balestrino A, Cervio G, Nava S, Moscato G: Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis. Am J Respir Crit Care Med 2006,173(3):310–317.CrossRefPubMed Pignatti P, Brunetti G, Moretto D, Yacoub MR, Fiori M, Balbi B, Balestrino A, Cervio G, Nava S, Moscato G: Role of the chemokine receptors CXCR3 and CCR4 in human pulmonary fibrosis. Am J Respir Crit Care Med 2006,173(3):310–317.CrossRefPubMed
11.
go back to reference Inoue T, Fujishima S, Ikeda E, Yoshie O, Tsukamoto N, Aiso S, Aikawa N, Kubo A, Matsushima K, Yamaguchi K: CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis. Eur Respir J 2004,24(1):49–56.CrossRefPubMed Inoue T, Fujishima S, Ikeda E, Yoshie O, Tsukamoto N, Aiso S, Aikawa N, Kubo A, Matsushima K, Yamaguchi K: CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis. Eur Respir J 2004,24(1):49–56.CrossRefPubMed
12.
go back to reference Watters LC, King TE, Schwarz MI, Waldron JA, Stanford RE, Cherniack RM: A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis. Am Rev Respir Dis 1986,133(1):97–103.CrossRefPubMed Watters LC, King TE, Schwarz MI, Waldron JA, Stanford RE, Cherniack RM: A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis. Am Rev Respir Dis 1986,133(1):97–103.CrossRefPubMed
13.
go back to reference Nakamura H, Fujishima S, Soejima K, Waki Y, Nakamura M, Ishizaka A, Kanazawa M: Flow cytometric detection of cell-associated cytokines in alveolar macrophages. Eur Respir J 1996,9(6):1181–1187.CrossRefPubMed Nakamura H, Fujishima S, Soejima K, Waki Y, Nakamura M, Ishizaka A, Kanazawa M: Flow cytometric detection of cell-associated cytokines in alveolar macrophages. Eur Respir J 1996,9(6):1181–1187.CrossRefPubMed
14.
go back to reference Nakamura H, Fujishima S, Waki Y, Urano T, Sayama K, Sakamaki F, Terashima T, Soejima K, Tasaka S, Ishizaka A, et al.: Priming of alveolar macrophages for interleukin-8 production in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1995,152(5 Pt 1):1579–1586.CrossRefPubMed Nakamura H, Fujishima S, Waki Y, Urano T, Sayama K, Sakamaki F, Terashima T, Soejima K, Tasaka S, Ishizaka A, et al.: Priming of alveolar macrophages for interleukin-8 production in patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1995,152(5 Pt 1):1579–1586.CrossRefPubMed
15.
go back to reference Wood GS, Warner NL, Warnke RA: Anti-Leu-3/T4 antibodies react with cells of monocyte/macrophage and Langerhans lineage. J Immunol 1983,131(1):212–216.PubMed Wood GS, Warner NL, Warnke RA: Anti-Leu-3/T4 antibodies react with cells of monocyte/macrophage and Langerhans lineage. J Immunol 1983,131(1):212–216.PubMed
16.
go back to reference Marchal-Somme J, Uzunhan Y, Marchand-Adam S, Valeyre D, Soumelis V, Crestani B, Soler P: Cutting edge: nonproliferating mature immune cells form a novel type of organized lymphoid structure in idiopathic pulmonary fibrosis. J Immunol 2006,176(10):5735–5739.CrossRefPubMed Marchal-Somme J, Uzunhan Y, Marchand-Adam S, Valeyre D, Soumelis V, Crestani B, Soler P: Cutting edge: nonproliferating mature immune cells form a novel type of organized lymphoid structure in idiopathic pulmonary fibrosis. J Immunol 2006,176(10):5735–5739.CrossRefPubMed
17.
go back to reference Penna G, Vulcano M, Sozzani S, Adorini L: Differential migration behavior and chemokine production by myeloid and plasmacytoid dendritic cells. Hum Immunol 2002,63(12):1164–1171.CrossRefPubMed Penna G, Vulcano M, Sozzani S, Adorini L: Differential migration behavior and chemokine production by myeloid and plasmacytoid dendritic cells. Hum Immunol 2002,63(12):1164–1171.CrossRefPubMed
18.
go back to reference Miyazaki E, Nureki S, Fukami T, Shigenaga T, Ando M, Ito K, Ando H, Sugisaki K, Kumamoto T, Tsuda T: Elevated levels of thymus- and activation-regulated chemokine in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia. Am J Respir Crit Care Med 2002,165(8):1125–1131.CrossRefPubMed Miyazaki E, Nureki S, Fukami T, Shigenaga T, Ando M, Ito K, Ando H, Sugisaki K, Kumamoto T, Tsuda T: Elevated levels of thymus- and activation-regulated chemokine in bronchoalveolar lavage fluid from patients with eosinophilic pneumonia. Am J Respir Crit Care Med 2002,165(8):1125–1131.CrossRefPubMed
19.
go back to reference Marchal-Somme J, Uzunhan Y, Marchand-Adam S, Kambouchner M, Valeyre D, Crestani B, Soler P: Dendritic cells accumulate in human fibrotic interstitial lung disease. Am J Respir Crit Care Med 2007,176(10):1007–1014.CrossRefPubMed Marchal-Somme J, Uzunhan Y, Marchand-Adam S, Kambouchner M, Valeyre D, Crestani B, Soler P: Dendritic cells accumulate in human fibrotic interstitial lung disease. Am J Respir Crit Care Med 2007,176(10):1007–1014.CrossRefPubMed
20.
go back to reference Sekiya T, Miyamasu M, Imanishi M, Yamada H, Nakajima T, Yamaguchi M, Fujisawa T, Pawankar R, Sano Y, Ohta K, et al.: Inducible expression of a Th2-type CC chemokine thymus- and activation-regulated chemokine by human bronchial epithelial cells. J Immunol 2000,165(4):2205–2213.CrossRefPubMed Sekiya T, Miyamasu M, Imanishi M, Yamada H, Nakajima T, Yamaguchi M, Fujisawa T, Pawankar R, Sano Y, Ohta K, et al.: Inducible expression of a Th2-type CC chemokine thymus- and activation-regulated chemokine by human bronchial epithelial cells. J Immunol 2000,165(4):2205–2213.CrossRefPubMed
21.
go back to reference Heijink IH, Marcel Kies P, van Oosterhout AJ, Postma DS, Kauffman HF, Vellenga E: Der p, IL-4, and TGF-beta cooperatively induce EGFR-dependent TARC expression in airway epithelium. Am J Respir Cell Mol Biol 2007,36(3):351–359.CrossRefPubMed Heijink IH, Marcel Kies P, van Oosterhout AJ, Postma DS, Kauffman HF, Vellenga E: Der p, IL-4, and TGF-beta cooperatively induce EGFR-dependent TARC expression in airway epithelium. Am J Respir Cell Mol Biol 2007,36(3):351–359.CrossRefPubMed
22.
go back to reference Berin MC, Eckmann L, Broide DH, Kagnoff MF: Regulated production of the T helper 2-type T-cell chemoattractant TARC by human bronchial epithelial cells in vitro and in human lung xenografts. Am J Respir Cell Mol Biol 2001,24(4):382–389.CrossRefPubMed Berin MC, Eckmann L, Broide DH, Kagnoff MF: Regulated production of the T helper 2-type T-cell chemoattractant TARC by human bronchial epithelial cells in vitro and in human lung xenografts. Am J Respir Cell Mol Biol 2001,24(4):382–389.CrossRefPubMed
23.
go back to reference Manabe K, Nishioka Y, Kishi J, Inayama M, Aono Y, Nakamura Y, Ogushi F, Bando H, Tani K, Sone S: Elevation of macrophage-derived chemokine in eosinophilic pneumonia: a role of alveolar macrophages. J Med Invest 2005,52(1–2):85–92.CrossRefPubMed Manabe K, Nishioka Y, Kishi J, Inayama M, Aono Y, Nakamura Y, Ogushi F, Bando H, Tani K, Sone S: Elevation of macrophage-derived chemokine in eosinophilic pneumonia: a role of alveolar macrophages. J Med Invest 2005,52(1–2):85–92.CrossRefPubMed
24.
go back to reference Kuroda E, Sugiura T, Okada K, Zeki K, Yamashita U: Prostaglandin E2 up-regulates macrophage-derived chemokine production but suppresses IFN-inducible protein-10 production by APC. J Immunol 2001,166(3):1650–1658.CrossRefPubMed Kuroda E, Sugiura T, Okada K, Zeki K, Yamashita U: Prostaglandin E2 up-regulates macrophage-derived chemokine production but suppresses IFN-inducible protein-10 production by APC. J Immunol 2001,166(3):1650–1658.CrossRefPubMed
25.
go back to reference Fireman E, Ben Efraim S, Greif J, Alguetti A, Ayalon D, Topilsky M: Suppressive activity of alveolar macrophages and blood monocytes from interstitial lung diseases: role of released soluble factors. Int J Immunopharmacol 1989,11(7):751–760.CrossRefPubMed Fireman E, Ben Efraim S, Greif J, Alguetti A, Ayalon D, Topilsky M: Suppressive activity of alveolar macrophages and blood monocytes from interstitial lung diseases: role of released soluble factors. Int J Immunopharmacol 1989,11(7):751–760.CrossRefPubMed
26.
go back to reference Trujillo G, O'Connor EC, Kunkel SL, Hogaboam CM: A novel mechanism for CCR4 in the regulation of macrophage activation in bleomycin-induced pulmonary fibrosis. Am J Pathol 2008,172(5):1209–1221.CrossRefPubMedPubMedCentral Trujillo G, O'Connor EC, Kunkel SL, Hogaboam CM: A novel mechanism for CCR4 in the regulation of macrophage activation in bleomycin-induced pulmonary fibrosis. Am J Pathol 2008,172(5):1209–1221.CrossRefPubMedPubMedCentral
Metadata
Title
Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis
Authors
Yurika Yogo
Seitaro Fujishima
Takashi Inoue
Fumitake Saito
Takayuki Shiomi
Kazuhiro Yamaguchi
Akitoshi Ishizaka
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2009
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-10-80

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