CHEST COPD COPD CXCR3 CCR5 Claudia Costa, MD; Rogerio Rufino, MD; Suzanne L. Traves, PhD;Jose Roberto Lapa e Silva, MD; Peter J. Barnes, DSc, FCCP; and Louise E. Donnelly, PhD COPD CD4 CD8 T CXCR3 CCR5 COPD CXCR3 CXCL9 CXCL1 CXCL11 CCR5 CCL5 (n = 18) (n = 2) COPD (n = 35) (ELISA) CXCL9 CXCL1 CXCL11 CCL5 COPD CXCL9 CXCL1 CXCL11 CCL5 CXCL9 14.3 pg / ml (IQR 6.5 99.3) 1.4pg/mL(IQR 1.4) (P.1) 8.5pg/mL(IQR 16.) CXCL1 16.9pg/mL(IQR 6.2 148.8) 3.7 pg / ml (IQR 18.8) (P.5) 11.3 pg / ml (IQR 3.7 46.7) CXCL11 58.1 pg / ml (IQR 34.5 85.3) 33.5 pg / ml (IQR 23.2 49.7) (P.5) 49.8 pg / ml (IQR 32.6 15.6) CCL5 59.9 pg / ml (IQR 57.1 67.8) 33.5 pg / ml (IQR 31.6 36.9) (P.1) CCL5 63. pg / ml (IQR 6.8 7.2) P.1 FEV 1 FEV 1 /FVC CXCR3 CCL5 COPD COPD 36
CCR5; (chemokines); (COPD); CXCR3; (sputum) DTT = dithiothreitol; ELISA = enzyme-linked immunosorbent assay; GOLD = Global Initiative for Chronic Obstructive Lung Disease; IFN = interferon; IQR = interquartile range COPD [1 2] T [3] CD4 CD8 [4] COPD [5] T COPD CD4 /CD8 T CD8 [3,4] COPDT CXCR3 CCR5 [6] COPD CXCR3 CXCL1 ( 1 kd IFN ) [7,8] CXCR3 CD8 From Airway Disease (Drs. Costa, Rufino, Traves, Barnes, and Donnelly), National Heart and Lung Institute, Imperial College London, London, UK; and Laboratorio Multidisciplinar de Pesquisa (Dr. Lapa e Silva), Hospital Universitrio Clementino Fraga Filho/Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. This study was supported by the National Heart and Lung Institute, London, UK; Committee for Postgraduate Courses in Higher Education, Brazil; and National Council for Scientific and Technological Development, Brazil. Correspondence to: Louise E. Donnelly, PhD, Airway Disease, National Heart and Lung Institute, Dovehouse St, London,SW3 6LY, UK; e-mail: l.donnelly@imperial.ac.uk COPD CD8 [7] CXCR3 B COPDB [1] CXCR3 12 [6] COPD T COPD CCR5 RANTES ( T ) / CCL5 1α (CCL3) 1β (CCL4) [9] CXCR3 3 IFN γ (CXCL9) CXCL1 IFN T α (CXCL11) [1] CXCL11 [11] CXCR3 CCR3 [12] CXCL11 CCR5 [13] CXCL9 [14] CXCR3 T CXCL9 CXCL1 CXCL11 CCL5 IFN γ COPD Th1 / Tc1 [15] COPD CXCR3 IFN γ 3 CXCR3 [16] COPD [17] CXCL1 www.chestjournal.org.cn CHEST 28 5 5 5 37
1 (1) COPD / / 8/1 13/7 22/13 / 39.7 2.3 5.8 2.8 63.4 1.7 (2 3) / y 28. 3.1 38. 2.5 FEV 1 /% 13 3.7 95.3 3.8 59.3 4.5 (2 4) FEV 1 /FVC 82.6 1.6 77. 1.3 55.2 1.6 (2 4) (1) (2) COPD P.1 (3) COPD P.1 (4) COPD P.1 [18] [9] CXCR3 CCR5 COPD COPD CXCL9 CXCL1 CXCL11 CCL5 Rio de Janeiro Clementino Fraga Filho Rio de Janeiro Pedro Ernesto Rio de Janeiro Brompton Harefield COPD (GOLD) [19] 4wk COPD Pin [2] 4 µg (Ultra-NEB 99 Devilbiss Somerse PA) 3% 4% 5% ( / ) 7min (PEF) 1% 2 COPD (1) COPD /x1 5 541. (374.5 73.) 634.5 (392.5 734.5) 549. (411. 725.) /x1 5 165. (87.5 266.5) 173.5 (13. 247.) 122. (64. 191.) / % 62.2 (41.4 8.4) 43.5 (28.9 66.4) 3. (19. 53.) (3) /x1 5 16. (49.5 2.) 173. (6.5 379.5) 29. (16. 411.) / % 35.2 (2.3 57.9) 5.1 (3. 7.1) 68 (3 75.) /x1 5. (. 4.) 1.5 (. 6.5) 4. (2. 23.) (3) /x1 5.5 (. 1.). (. 1.5) 2. (. 5.) (2) CD4 + /x1 5. (. 1.). (. 1.). (. 1.) CD8 + /x1 5. (. 1.). (. 1.) 1. (. 4.) (2 3) /x1 5 1.5 (. 3.). (. 2.). (. 3.) (1) (IQR) (2) COPD P.5 (3) COPD P.1 38
3 DTT (1) CCL5 CXCL9 CXCL1 CXCL11 FEV 1 /%.38 (3).45 (4).27 (2).3 (3) FEV 1 /FVC.39 (4).48 (4).27 (2).37 (3).32 (3).31 (3).29 (2).28 (2) /%.31 (3).24 (2).29 (2).33 (3).19.9.29 (2).3 /%.42 (4).32 (3).44 (4).26 (2) (1) Spearman (2) P.5 (3) P.1 (4) P.1 2h (3 g) 4 (DTT).1% ( / ) 1 min 4 Dulbecco.5% ( / ) DTT 5min (3 g) 7 1. 1 6 /ml ( 3 shandon cheshire UK) Diff- Quick (Laborclin Pinhais Brazil) T CD4 (Sigma Chemical St. Louis MO) CD8 (Sigma Chemical) CCL5 CXCL9 CXCL1 CXCL1 (ELISA) (R&D Systems Minneapolis MN) DTT DTT 7.8pg/mL GraphPad Prism (GraphPad Softwate San Diego CA) STATA 8. (StataCorp LP College Station TX) (IQR) CXCL9 CXCL1 CXCL9 / pg ml -1 CXCL1 / pg ml -1 CXCL11 / pg ml -1 1 3 5 2 5 1 8 6 4 2 4 2 1 5 1 5 4 1 5 4 3 2 1 A B C (n = 18) (n = 2) COPD (n = 35) COPD CXCR3 COPD ELISA CXCL9 (A) CXCL1 (B) CXCL11 (C) * P.5 *** P.1 www.chestjournal.org.cn CHEST 28 5 5 5 39
Tobit CXCL11 CCL5 P.5 15 A COPD FEV 1 FEV 1 /FVC ( 1) COPD COPD 6 GOLD CCL5 / pg ml -1 1 5 (n = 18) (n = 2) COPD (n = 35) 13 12 4 B 9 COPD CD8 T ( ) CD8 T COPD CCL5 / pg ml -1 7 ( 3) COPD ( 3) 5 GOLD (n =6) GOLD (n = 13) GOLD + (n =16) CXCR3 CXCR3CXCL9 1.4 pg / ml (IQR 1.4) 8.5 pg / ml (IQR 6.) COPD 14.3 pg / ml (IQR 6.5 99.3) CXCL1 3.7 pg / ml (IQR 18.8) 11.3 pg / ml (IQR 3.7 46.7) COPD 16.9pg/mL(IQR 6.2 148.8)CXCL11 33.5 pg / ml (IQR 23.2 49.7) 49.8 pg / ml (IQR 32.6 15.6) COPD 58.1 pg / ml (IQR 34.4 85.3) COPD 2 COPD CCL5 COPD ELISA CCL5 A CCL5 ( DTT) B COPD CCL5 (GOLD ) ** P.1 *** P.1 COPD 33.5 pg / ml (IQR 31.6 36.9) 63.pg/mL(IQR 6.8 7.2) COPD 6.4 pg / ml (IQR 57. 68.5) ( 2A) CCL5 ( 1) COPD COPD COPD CCL5 CCL5 CCL5 GOLD (GOLD 31
) CCL5 ( 2B) COPD ( ) CXCL9 CXCL1 CXCL11 CCL5 CCL5 CXCL9 CXCL1 CXCL11 (FEV 1 FEV 1 /FVC) ( 3 3) CCL5 CXCL9 CXCL1 CXCL11 ( 3) CXCL1 () CCL5 CXCL9 CXCL11 ( CXCL9 / pg ml -1 3 5 2 5 1 5 1 5 A CXCL1 / pg ml -1 3 5 2 5 2 1 5 1 5 1 5 B CXCL11 / pg ml -1 3 5 2 5 1 5 5 4 3 2 1 C CCL5 / pg ml -1 1 5 D 2 6 1 2 6 1 FEV 1 /% 3 FEV 1 FEV 1 CXCL9 (A) FEV 1 CXCL1 (B) FEV 1 CXCL11 (C) FEV 1 CCL5 (D) COPD www.chestjournal.org.cn CHEST 28 5 5 5 311
4 COPD (1) CCL5 CXCL9 CXCL1 CXCL11 FEV 1 /%.62 (4).39 (2).2.26 FEV 1 /FVC.43 (2).19.12.25.33.15.19.4 (2) / %.26.33.37 (2).19.11.28.35 (2).8 /%.47 (4).31.43 (4).21.26.44 (4).6.8 CD4 +.1.35 (2).7.11 CD8 +.3.44 (4).6.9 (1) Spearman (2) P.5 COPD COPD CXCR3 COPD () [3] COPD CXCL9 [27] CXCR3 [28] (3) P.1 (4) P.1 COPD r =.38 r =38 r =.23) COPD CXCL9 CXCL1 CXCL11 ( 4) CCL5 CXCL1 ( 4) COPD [21-23] [24] DTT [25,26] COPD CXCR3 CXCR3 CCL5 (FEV 1 FEV 1 /FVC) CXCR3 GOLD COPD COPD CCL5 CXCR3 T [29] COPD COPD ( ) COPD CXCL11 CXCL11 CXCR3 CXCR3 T CXCR3 CXCL11 T COPD COPD CXCR3 [31] COPD [1] CXCR3 COPD CD8 T CD8 312
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