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Vol. 137, No. 3, 2005
Issue release date: July 2005
Int Arch Allergy Immunol 2005;137:229–235

Accumulation of CXCR3-Expressing Eosinophils and Increased Concentration of Its Ligands (IP10 and Mig) in Bronchoalveolar Lavage Fluid of Patients with Chronic Eosinophilic Pneumonia

Katoh S. · Fukushima K. · Matsumoto N. · Ehara N. · Matsumoto K. · Yamauchi A. · Hirashima M.
Departments of aCell Regulation and bImmunology and Immunopathology, School of Medicine, Kagawa University, Kagawa, cNagasaki Prefecture Tarami Hospital, Nagasaki, and dThird Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan

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Background: Since human peripheral eosinophils have been shown to migrate to the CXC chemokine receptor 3 (CXCR3) ligands IFN-γ-inducible protein 10 (IP10) and monokine induced by IFN-γ (Mig), this confirms that CXCR3 is functionally expressed on these cells. IP10 expression has been shown to be increased in the airways of asthmatics. Eosinophil accumulations are found in bronchoalveolar lavage fluid (BALF) from patients with chronic eosinophilic pneumonia (CEP). To examine the contribution of IP10 and Mig in the pathogenesis of CEP, we measured the concentration of IP10 and Mig, and evaluated the expression of CXCR3 on eosinophils in BALF taken from patients with CEP. Methods: The concentrations of IP10 and Mig in BALF were measured by ELISA. The proportion of CXCR3-expressing CD4+ T cells and CD16-negative eosinophils was determined by flow cytometry. Results: The BALF concentrations of IP10 and Mig were higher in patients with CEP, as well as in patients with sarcoidosis, when compared to healthy controls. The absolute number of CXCR3+ CD4+ T cells was significantly higher in the BALF of patients with sarcoidosis, but not in the patients with CEP, when compared to healthy volunteers. There were higher percentages of CXCR3-expressing eosinophils in the BALF than in the peripheral blood of patients with CEP. Conclusions: Our findings suggest that IP10 and Mig contribute to the accumulation of CXCR3-expressing eosinophils in the lungs of patients with CEP, and modulate the eosinophilic inflammation of the lung.

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  1. Carrington CB, Addington WW, Goff AM, Madoff IM, Marks A, Schwaber JR, Gaensler EA: Chronic eosinophilic pneumonia. N Engl J Med 1969;280:787–798.
  2. Fox B, Seed WA: Chronic eosinophilic pneumonia. Thorax 1980;35:570–580.
  3. Naughton M, Fahy J, FitzGerald MX: Chronic eosinophilic pneumonia: A long-term follow-up of 12 patients. Chest 1993;103:162–165.
  4. Kita H, Sur S, Hunt LW, Edell ES, Weiler DA, Swanson MC, Samsel RW, Abrams JS, Gleich GJ: Cytokine production at the site of disease in chronic eosinophilic pneumonia. Am J Respir Crit Care Med 1996;153:1437–1441.
  5. 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;165:1125–1131.
  6. 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;58:518–523.
  7. Katoh S, Matsumoto N, Matsumoto K, Fukushima K, Matsukura S: Elevated interleukin-18 levels in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia. Allergy 2004;59:850–856.
  8. Miotto D, Christodoulopoulos P, Olivenstein R, Taha R, Cameron L, Tsicopoulos A, Tonnel AB, Fahy O, Lafitte JJ, Luster AD, Wallaert B, Mapp CE, Hamid Q: Expression of IFN-γ-inducible protein; monocyte chemotactic proteins 1, 3, and 4; and eotaxin in Th1- and Th2-mediated lung diseases. J Allergy Clin Immunol 2001;107:664–670.
  9. Katoh S, Matsumoto N, Fukushima K, Mukae H, Kadota J, Kohno S, Matsukura S: Elevated chemokine levels in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia. J Allergy Clin Immunol 2000;106:730–736.
  10. Luster AD: Chemokines – chemotactic cytokines that mediate inflammation. N Engl J Med 1998;338:436–445.
  11. Sauty A, Dziejman M, Taha RA, Iarossi AS, Neote K, Garcia-Zepeda EA, Hamid Q, Luster AD: The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells. J Immunol 1999;162:3549–3558.
  12. Weng Y, Siciliano SJ, Waldburger KE, Sirotina-Meisher A, Staruch MJ, Daugherty BL, Gould SL, Springer MS, DeMartino JA: Binding and functional properties of recombinant and endogenous CXCR3 chemokine receptors. J Biol Chem 1998;273:18288–18291.
  13. Qin S, Rottman JB, Myers P, Kassam N, Weinblatt M, Loetscher M, Koch AE, Moser B, Mackay CR: The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J Clin Invest 1998;101:746–754.
  14. Sallusto F, Lenig D, Mackay CR, Lanzavecchia A: Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 1998;187:875–883.
  15. Bonecchi R, Bianchi G, Panina-Bordignon P, D’Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F: Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 1998;187:129–134.
  16. Piali L, Weber C, LaRosa G, Mackay CR, Springer TA, Clark-Lewis I, Moser B: The chemokine receptor CXCR3 mediates rapid and shear-resistant adhesion-induction of effector T lymphocytes by the chemokines IP10 and Mig. Eur J Immunol 1998;28:961–972.
  17. Patel DD, Zachariah JP, Whichard LP: CXCR3 and CCR5 ligands in rheumatoid arthritis synovium. Clin Immunol 2001;98:39–45.
  18. Agostini C, Cassatella M, Zambello R, Trentin L, Gasperini S, Perin A, Piazza F, Siviero M, Facco M, Dziejman M, Chilosi M, Qin S, Luster AD, Semenzato G: Involvement of the IP-10 chemokine in sarcoid granulomatous reactions. J Immunol 1998;161:6413–6420.
  19. Bochner BS, Hudson SA, Xiao HQ, Liu MC: Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late-phase reactions. J Allergy Clin Immunol 2003;112:930–934.
  20. Jinquan T, Jing C, Jacobi HH, Reimert CM, Millner A, Quan S, Hansen JB, Dissing S, Malling HJ, Skov PS, Poulsen LK: CXCR3 expression and activation of eosinophils: Role of IFN-γ-inducible protein-10 and monokine induced by IFN-γ. J Immunol 2000;165:1548–1556.
  21. Kadota J, Matsubara Y, Ishimatsu Y, Ashida M, Abe K, Shirai R, Iida K, Kawakami K, Taniguchi H, Fujii T, Kaseda M, Kawamoto S, Kohno S: Significance of IL-1β and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB). Clin Exp Immunol 1996;103:461–466.
  22. Hansel TT, Pound JD, Pilling D, Kitas GD, Salmon M, Gentle TA, Lee SS, Thompson RA: Purification of human blood eosinophils by negative selection using immunomagnetic beads. J Immunol Methods 1989;122:97–103.
  23. Katoh S, Taniguchi H, Matsubara Y, Matsumoto N, Fukushima K, Kadota J, Matsukura S, Kohno S: Overexpression of CD44 on alveolar eosinophils with high concentrations of soluble CD44 in bronchoalveolar lavage fluid in patients with eosinophilic pneumonia. Allergy 1999;54:1286–1292.
  24. Medoff BD, Sauty A, Tager AM, Maclean JA, Smith RN, Mathew A, Dufour JH, Luster AD: INF-γ-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma. J Immunol 2002;168:5278–5286.
  25. Tateno H, Nakamura H, Minematsu N, Amakawa K, Terashima T, Fujishima S, Luster AD, Lilly CM, Yamaguchi K: Eotaxin and monocyte chemoattractant protein-1 in chronic eosinophilic pneumonia. Eur Respir J 2001;17:962–968.
  26. Loetscher P, Pellegrino A, Gong J-H, Mattioli I, Loetscher M, Bardi G, Baggiolini M, Clark-Lewis I: The ligands of CXC chemokine receptor 3, I-TAC, Mig, and IP10, are natural antagonists for CCR3. J Biol Chem 2001;276:2986–2991.
  27. Xanthou G, Duchesnes CE, Williams TJ, Pease JE: CCR3 functional responses are regulated by both CXCR3 and its ligands CXCL9, CXCL10 and CXCL11. Eur J Immunol 2003;33:2241–2250.
  28. Fulkerson PC, Zimmermann N, Brandt EB, Muntel EE, Doepker MP, Kavanaugh JL, Mishra A, Witte DP, Zhang H, Farber JM, Yang M, Foster PS, Rothenberg ME: Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by IFN-γ (Mig, CXCL9). Proc Natl Acad Sci USA 2004;101:1987–1992.
  29. Liu LY, Jarjour NN, Busse WW, Kelly EAB: Chemokine receptor expression on human eosinophils from peripheral blood and bronchoalveolar lavage fluid after segmental antigen challenge. J Allergy Clin Immunol 2003;112:556–562.
  30. Nagase H, Kudo K, Izumi S, Ohta K, Kobayashi N, Yamaguchi M, Matsushima K, Morita Y, Yamamoto K, Hirai K: Chemokine receptor expression profile of eosinophils at inflamed tissue sites: Decreased CCR3 and increased CXCR4 expression by lung eosinophils. J Allergy Clin Immunol 2001;108:563–569.
  31. Thomas MS, Kunkel SL, Lukacs NW: Differential role of IFN-γ-inducible protein 10 kDa in a cockroach antigen-induced model of allergic airway hyperreactivity: Systemic versus local effects. J Immunol 2002;169:7045–7053.

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