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Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor–dependent pathway  Chun-Hua.

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Presentation on theme: "Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor–dependent pathway  Chun-Hua."— Presentation transcript:

1 Increased activation of fibrocytes in patients with chronic obstructive asthma through an epidermal growth factor receptor–dependent pathway  Chun-Hua Wang, MD, Chien-Da Huang, MD, Horng-Chyuan Lin, MD, Tzu-Ting Huang, BS, Kang-Yun Lee, MD, PhD, Yu-Lun Lo, MD, Shu-Min Lin, MD, Kian Fan Chung, MD, DSc, Han-Pin Kuo, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 129, Issue 5, Pages (May 2012) DOI: /j.jaci Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 A, Flow cytometric analysis of NANT cells immunostained for collagen I, CD45, and EGFR. B, Percentages of CD45+/collagen I+/EGFR+ fibrocytes and EGFR expression in CD45+/collagen I+ as mean fluorescence intensity. Horizontal lines are mean values. C, Confocal image analysis of phosphorylated EGFR in CD34+ and CD45+ fibrocytes. D, Individual percentage of fibrocytes expressing human epidermal receptors (Her) 1, 2, and 3. *P < .05 and **P < .01 compared with healthy subjects. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 A, Spindle-shaped myofibroblasts from patients with COA receiving AG1478 (×200 magnification). B, Effect of the EGFR tyrosine kinase inhibitor AG1478 on the α-SMA+ myofibroblasts from healthy subjects (n = 9) or asthmatic patients with NPF (n = 12) or COA (n = 12). *P < .05 and **P < .01 compared without AG1478. C, Effect of gefitinib (1 μmol/L) on fibrocytes and myofibroblasts from asthmatic patients with NPF (n = 6) and COA (n = 8). *P < .05. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 A, Example of flow cytometric analysis of ADAM17 and collagen I expression on CD45+ cells. B, CD45+/collagen I+/ADAM 17+ fibrocytes (left) and ADAM17 activity as mean fluorescence intensity (right) in healthy subjects (n = 14) or asthmatic patients with NPF (n = 16) or COA (n = 16). C, Fibrocytes and myofibroblasts from patients with NPF (n = 8) and COA (n = 9) incubated with TAPI-1. Data are presented as means ± SEMs. *P < .05. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 A, Flow cytometric histogram of ADAM17 expression after transfection with ADAM17 (red), scrambled siRNA (blue), or IgG (black). B, Percentage of ADAM17+ fibrocytes after ADAM17 or scrambled siRNA knock down (n = 5). Maximum to minimum, 25% to 75% percentiles as boxes, and medians are shown. *P < .05. C, Transfection with ADAM17 siRNA decreased fibrocyte proliferation (left) and myofibroblast transformation (right). Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Effect of NAC on the expression of EGFR (A) and ADAM17 (B) on fibrocytes from patients with COA (n = 6). Effect of NAC on fibrocyte proliferation (C) and transformation into myofibroblasts (D) of patients with COA (n = 7) for 14 days. Data represent means ± SEMs. *P < .05 and **P < .01. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 A and B, Effect of H2O2 on EGFR expression (Fig 6, A; n = 7) and ADAM17 (Fig 6, B; n = 7) on fibrocytes from asthmatic patients with NPF and of NAC on the expression of EGFR and ADAM17. *P < .05 and **P < .01 compared with vehicle. +P < .05. C and D, Effects of H2O2 , NAC, or gefitinib on fibrocyte proliferation (Fig 6, C) and transformation into myofibroblasts (Fig 6, D). *P < .05 compared with vehicle. +P < .05. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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