Eotaxin and the attraction of eosinophils to the asthmatic lung

Respiratory Research

Timothy J Williams¹  Dolores M Conroy¹ 

[1] Leukocyte Biology Section, Biomedical Sciences Division, Imperial College School of Medicine, London, UK

关键词: eotaxin;    eosinophils;    chemokines;    asthma;    allergy;   

Others  :  1227453
DOI  :  10.1186/rr52

 received in 2001-02-06, accepted in 2001-03-01,  发布年份 2001

【 摘 要 】

Eosinophilic leukocytes accumulate in high numbers in the lungs of asthmatic patients, and are believed to be important in the pathogenisis of asthma. A potent eosinophil chemoattractant is produced in the asthmatic lung. This small protein, the chemokine eotaxin, is synthesized by a number of different cell types, and is stimulated by interleukin-4 and interleukin-13, which are produced by T-helper (Th)2 lymphocytes. Low molecular weight compounds have been developed that can block the eotaxin receptor C-C chemokine receptor (CCR)3, and prevent stimulation by eotaxin. This provides the potential for orally available drugs that can prevent eosinophil recruitment into the lung and the associated damage and dysfunction.

【 授权许可】

   
2001 BioMed Central Ltd

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Ehrlich P: Ueber die specifischen granulationen des Blutes [in German]. Arch Anat Physiol 1879, 3:571.
• [2]Huber HL, Koessler KK: The pathology of bronchial asthma. Arch Intern Med 1922, 30:689-760.
• [3]Griffiths-Johnson DA, Collins PD, Rossi AG, Jose PJ, Williams TJ: The chemokine, eotaxin, activates guinea-pig eosinophils in vitro, and causes their accumulation into the lung in vivo. Biochem Biophys Res Commun 1993, 197:1167-1172.
• [4]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, 179:881-887.
• [5]Jose PJ, Adcock IM, Griffiths-Johnson DA, Berkman N, Wells TNC, Williams TJ, Power CA: Eotaxin: cloning of an eosinophil chemoattractant cytokine and increased mRNA expression in allergen-challenged guinea-pig lungs. Biochem Biophys Res Commun 1994, 205:788-794.
• [6]Rothenberg ME, Luster AD, Lilly CM, Drazen JM, Leder P: Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung. J Exp Med 1995, 181:1211-1216.
• [7]Gonzalo J-A, Jia G-Q, Aguirre V, Friend D, Coyle AJ, Jenkins NA, Lin G-S, Katz H, Lichtman A, Copeland N, Kopf M, Gutierrez-Ramos J-C: Mouse eotaxin expression parallels eosinophil accumulation during lung allergic inflammation but it is not restricted to a Th2-type response. Immunity 1996, 4:1-14.
• [8]Williams CMM, Newton DJ, Wilson SA, Williams TJ, Coleman JW, Flanagan BF: Conserved structure and tissue expression of rat eotaxin. Immunogenetics 1998, 47:178-180.
• [9]Ishi Y, Shirato M, Nomura A, Sakamoto T, Uchida Y, Ohtsuka M, Sagai M, Hasegawa S: Cloning of rat eotaxin: ozone inhalation increases mRNA and protein expression in lungs of Brown Norway rats. Am J Physiol 1998, 274:L171-L176.
• [10]Benarafa C, Cunningham FM, Hamblin AS, Horohov DW, Collins ME: Cloning of equine chemokines eotaxin, monocyte chemoattractant protein (MCP)-1, MCP-2 and MCP-4, mRNA expression in tissues and induction by IL-4 in dermal fibroblasts. Vet Immunol Immunopathol 2000, 76:283-298.
• [11]Ponath PD, Qin S, Ringler DJ, Clark-Lewis I, Wang J, Kassam N, Smith H, Shi X, Gonzalo J-A, Newman W, Gutierrez-Ramos J-C, Mackay CR: Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding and functional properties suggest a mechanism for the selective recruitment of eosinophils. J Clin Invest 1996, 97:604-612.
• [12]Garcia-Zepeda EA, Rothenberg ME, Ownbey RT, Celestin J, Leder P, Luster AD: Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia. Nature Med 1996, 2:449-456.
• [13]Kitaura M, Nakajima T, Imai T, Harada S, Combadiere C, Tiffany HL, Murphy PM, Yoshie O: Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3. J Biol Chem 1996, 271:7725-7730.
• [14]Sabroe I, Conroy DM, Gerard NP, Li Y, Collins PD, Post TW, Jose PJ, Williams TJ, Gerard C, Ponath PD: Cloning and characterisation of the guinea pig eosinophil eotaxin receptor, CCR3: blockade using a monoclonal antibody in vivo. J Immunol 1998, 161:6139-6147.
• [15]Sanz M-J, Ponath PD, Mackay CR, Newman W, Miyasaka M, Tamatani T, Flanagan BF, Lobb RR, Williams TJ, Nourshargh S, Jose PJ: Human eotaxin induces α4 and β2 integrin-dependent eosinophil accumulation in rat skin in vivo : delayed generation of eotaxin in response to IL-4. J Immunol 1998, 160:3569-3576.
• [16]Forssmann U, Uguccioni M, Loetscher P, Dahinden CA, Langen H, Thelen M, Baggiolini M: Eotaxin-2, a novel CC chemokine that is selective for the chemokine receptor CCR3, and acts like eotaxin on human eosinophil and basophil leukocytes. J Exp Med 1997, 185:2171-2176.
• [17]White JR, Imburgia C, Dul E, Appelbaum E, O'Donnell K, O'Shannessy DJ, Brawner M, Fornwald J, Adamou J, Elshourbagy NA, Kaiser K, Foley JJ, Schmidt DB, Johanson K, Macphee C, Moores K, McNulty D, Scott GF, Schleimer RP, Sarau HM: Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils. J Leukoc Biol 1997, 62:667-675.
• [18]Shinkai A, Yoshisue H, Koike M, Shoji E, Nakagawa S, Saito A, Takeda T, Imabeppu S, Kato Y, Hanai N, Anazawa H, Kuga T, Nishi T: A novel human CC chemokine, eotaxin-3, which is expressed in IL-4-stimulated vascular endothelial cells, exhibits potent activity toward eosinophils. J Immunol 1999, 163:1602-1610.
• [19]Kitaura M, Suzuki N, Imai T, Takagi S, Suzuki R, Nakajima T, Hirai K, Nomiyama H, Yoshie O: Molecular cloning of a novel human CC chemokine (eotaxin-3) that is a functional ligand of CC chemokine receptor 3. J Biol Chem 1999, 274:27975-27980.
• [20]Zimmermann N, Hogan SP, Mishra A, Brandt EB, Bodette TR, Pope SM, Finkelman FD, Rothenberg ME: Murine eotaxin-2: a constitutive eosinophil chemokine induced by allergen challenge and IL-4 overexpression. J Immunol 2000, 165:5839-5846.
• [21]Ponath PD, Qin S, Post TW, Wang J, Wu L, Gerard NP, Newman W, Gerard C, Mackay CR: Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med 1996, 183:2437-2448.
• [22]Daugherty BL, Siciliano SJ, DeMartino J, Malkowitz L, Sirontino A, Springer MS: Cloning, expression and characterization of the human eosinophil eotaxin receptor. J Exp Med 1996, 183:2349-2354.
• [23]Gao J-L, Sen AI, Kitaura M, Yoshie O, Rothenberg ME, Murphy PM, Luster AD: Identification of a mouse eosinophil receptor for the CC chemokine eotaxin. Biochem Biophys Res Commun 1996, 223:679-684.
• [24]Heath H, Qin S, Wu L, LaRosa G, Kassam N, Ponath PD, Mackay CR: Chemokine receptor usage by human eosinophils. The importance of CCR3 demonstrated using an antagonistic monoclonal antibody. J Clin Invest 1997, 99:178-184.
• [25]Uguccioni M, Mackay CR, Ochensberger B, Loetscher P, Rhis S, LaRosa GJ, Rao P, Ponath PD, Baggiolini M, Dahinden CA: High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines. J Clin Invest 1997, 100:1137-1143.
• [26]Romagnani P, De Paulis A, Beltrame C, Annunziato F, Dente V, Maggi E, Romagnani S, Marone G: Tryptase-chymase double-positive human mast cells express the eotaxin receptor CCR3 and are attracted by CCR3-binding chemokines. Am J Pathol 1999, 155:1195-1204.
• [27]Sallusto F, Mackay CR, Lanzavecchia A: Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 1997, 277:2005-2007.
• [28]Lloyd CM, Delany T, Nguyen T, Tian J, Martinez-A C, Coyle AJ, Gutierrez-Ramos J-C: CC chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo. J Exp Med 2000, 191:265-273.
• [29]Zimmermann N, Conkright JJ, Rothenberg ME: CC chemokine receptor-3 undergoes prolonged ligand-induced internalization. J Biol Chem 1999, 274:12611-12618.
• [30]Humbles AA, Conroy DM, Marleau S, Rankin SM, Palframan RT, Proudfoot AEI, Wells TNC, Li D, Jeffery PK, Griffiths-Johnson DA, Williams TJ, Jose PJ: Kinetics of eotaxin generation and its relationship to eosinophil accumulation in allergic airways disease: analysis in a guinea pig model in vivo. J Exp Med 1997, 186:601-612.
• [31]Matthews AN, Friend DS, Zimmermann N, Sarafi MN, Luster AD, Pearlman E, Wert SE, Rothenberg ME: Eotaxin is required for the baseline level of tissue eosinophils. Proc Natl Acad Sci USA 1998, 95:6273-6278.
• [32]Teruya-Feldstein J, Jaffe ES, Burd PR, Kingma DW, Setsuda JE, Tosato G: Differential chemokine expression in tissues involved by Hodgkin's disease: direct correlation of eotaxin expression and tissue eosinophilia. Blood 1999, 93:2463-2470.
• [33]Rothenberg ME, MacLean JA, Pearlman E, Luster AD, Leder P: Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. J Exp Med 1997, 185:785-790.
• [34]Yang Y, Loy J, Ryseck RP, Carrasco D, Bravo R: Antigen-induced eosinophilic lung inflammation develops in mice deficient in chemokine eotaxin. Blood 1998, 92:3912-3923.
• [35]Gonzalo J-A, Lloyd CM, Wen D, Albar JP, Wells TNC, Proudfoot A, Martinez AC, Dorf M, Bjerke T, Coyle AJ, Gutierrez-Ramos J-C: The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airways hyperresponsiveness. J Exp Med 1998, 188:157-167.
• [36]Campbell EM, Kunkel SL, Strieter RM, Lukacs NW: Temporal role of chemokines in a murine model of cockroach allergen-induced airway hyperreactivity and eosinophilia. J Immunol 1998, 161:7047-7053.
• [37]Ying S, Robinson DS, Meng Q, Rottman J, Kennedy R, Ringler DJ, Mackay CR, Daugherty BL, Springer MS, Durham SR, Williams TJ, Kay AB: Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells. Eur J Immunol 1997, 27:3507-3516.
• [38]Lamkhioued B, Renzi PM, Younes A, Garcia-Zepeda EA, Allakhverdi Z, Ghaffar O, Rothenberg MD, Luster AD, Hamid QA: Increased expression of eotaxin in bronchoalveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation. J Immunol 1997, 159:4593-4601.
• [39]Mattoli S, Stacey MA, Sun G, Bellini A, Marini M: Eotaxin expression and eosinophilic inflammation in asthma. Biochem Biophys Res Commun 1997, 236:299-301.
• [40]Nakamura H, Weiss ST, Israel E, Luster AD, Drazen JM, Lilly CM: Eotaxin and impaired lung function in asthma. Am J Respir Crit Care Med 1999, 160:1952-1956.
• [41]Zeibecoglou K, Ying S, Meng Q, Kay AB, Robinson DS, Papa-georgiou N: Expression of eotaxin in induced sputum of atopic and nonatopic asthmatics. Allergy 2000, 55:1042-1048.
• [42]Minshall EM, Cameron L, Lavigne F, Leung DY, Hamilos D, Garcia Zepada EA, Rothenberg M, Luster AD, Hamid Q: Eotaxin mRNA and protein expression in chronic sinusitis and allergen-induced nasal responses in seasonal allergic rhinitis. Am J Respir Cell Mol Biol 1997, 17:683-690.
• [43]Ying S, Robinson DS, Meng Q, Barata LT, McEuen AR, Buckley MG, Walls AF, Askenase PW, Kay AB: C-C chemokines in allergen-induced late-phase cutaneous responses in atopic subjects: association of eotaxin with early 6-hour eosinophils, and of eotaxin-2 and monocyte chemoattractant protein-4 with the later 24-hour tissue eosinophilia, and relationship to basophils and other C-C chemokines (monocyte chemoattractant protein-3 and RANTES). J Immunol 1999, 163:3976-3984.
• [44]MacLean JA, Ownbey R, Luster AD: T cell-dependent regulation of eotaxin in antigen-induced pulmonary eosinophilia. J Exp Med 1996, 184:1461-1469.
• [45]Rothenberg ME, Luster AD, Leder P: Murine eotaxin: an eosinophil chemoattractant inducible in endothelial cells and in interleukin 4-induced tumor suppression. Proc Natl Acad Sci USA 1995, 92:8960-8964.
• [46]Ruth JH, Lukacs NW, Warmington KS, Polak TJ, Burdick M, Kunkel SL, Strieter RM, Chensue SW: Expression and participation of eotaxin during mycobacterial (type 1) and schistosomal (type 2) antigen-elicited granuloma formation. J Immunol 1998, 161:4276-4282.
• [47]Li L, Xia Y, Nguyen A, Lai YH, Feng L, Mosmann TR, Lo D: Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. J Immunol 1999, 162:2477-2487.
• [48]Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, Zhang Y, Elias JA: Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999, 103:779-788.
• [49]Teran LM, Mochizuki M, Bartels J, Valencia EL, Nakajima T, Hirai K, Schroder JM: Th1- and Th2-type cytokines regulate the expression and production of eotaxin and RANTES by human lung fibroblasts. Am J Respir Cell Mol Biol 1999, 20:777-786.
• [50]Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ: Control of TH2 polarization by the chemokine monocyte chemoattractant protein-1. Nature 2000, 404:407-411.
• [51]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.
• [52]Loetscher P, Pellegrino A, Gong JH, 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 2000, 276:2986-2991.
• [53]Collins PD, Marleau S, Griffiths-Johnson DA, Jose PJ, Williams TJ: Co-operation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 1995, 182:1169-1174.
• [54]Palframan RT, Collins PD, Severs NJ, Rothery S, Williams TJ, Rankin SM: Mechanisms of acute eosinophil mobilization from the bone marrow stimulated by interleukin 5: the role of specific adhesion molecules and phosphatidylinositol 3-kinase. J Exp Med 1998, 188:1621-1632.
• [55]Palframan RT, Collins PD, Williams TJ, Rankin SM: Eotaxin induces a rapid release of eosinophils and their progenitors from the bone marrow. Blood 1998, 91:2240-2248.
• [56]Culley FJ, Brown A, Conroy DM, Sabroe I, Pritchard DI, Williams TJ: Eotaxin is specifically cleaved by hookworm metalloproteases preventing its action in vitro and in vivo. J Immunol 2000, 165:6447-6453.
• [57]Marleau S, Griffiths-Johnson DA, Collins PD, Bakhle YS, Williams TJ, Jose PJ: Human RANTES acts as a receptor antagonist for guinea pig eotaxin in vitro and in vivo. J Immunol 1996, 157:4141-4146.
• [58]Teixeira MM, Wells TNC, Lukacs NW, Proudfoot AEI, Kunkel SL, Williams TJ, Hellewell PG: Chemokine-induced eosinophil recruitment. Evidence of a role for endogenous eotaxin in an in vivo allergy model in mouse skin. J Clin Invest 1997, 100:1657-1666.
• [59]Nibbs RJ, Salcedo TW, Campbell JD, Yao XT, Li Y, Nardelli B, Olsen HS, Morris TS, Proudfoot AE, Patel VP, Graham GJ: C-C chemokine receptor 3 antagonism by the beta-chemokine macrophage inflammatory protein 4, a property strongly enhanced by an amino-terminal alanine-methionine swap. J Immunol 2000, 164:1488-1497.
• [60]Sabroe I, Peck MJ, Jan Van Keulen B, Jorritsma A, Simmons G, Clapham PR, Williams TJ, Pease JE: A small molecule antagonist of the chemokine receptors CCR1 and CCR3: potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry. J Biol Chem 2000, 275:25985-25992.
• [61]Sabroe I, Hartnell A, Jopling LA, Bel S, Ponath PD, Pease JE, Collins PD, Williams TJ: Differential regulation of eosinophil chemokine signalling via CCR3 and non-CCR3 pathways. J Immunol 1999, 162:2946-2955.
• [62]White JR, Lee JM, Dede K, Imburgia CS, Jurewicz AJ, Chan G, Fornwold JA, Dhanak D, Christmann LT, Darcy MG, Widdowson KL, Foley JJ, Schmidt DB, Sarau HM: Identification of potent, selective non-peptide CCR3 antagonist that inhibits eotaxin-, eotaxin-2 and MCP-4 induced eosinophil migration. J Biol Chem 2000, 275:36626-36631.