title: Fibrocyte trafficking in patients with chronic obstructive asthma and during an acute asthma exacerbation.
abstract: BACKGROUND
  Fibrocytes express several chemokine receptors (CCR7 and CXCR4) that regulate their recruitment and trafficking into tissue-damage sites in response to specific chemokine gradients (CCL19 and CXCL12).
  
  
  OBJECTIVE
  We investigated whether these chemoattractants and S100A9, through the receptor for advanced glycation end-products (RAGE; ie, its receptor), are involved in fibrocyte trafficking in patients with chronic obstructive asthma (COA) and during an acute exacerbation (AE) in patients without airflow obstruction (Asthma AE group).
  
  
  METHODS
  We collected peripheral blood from 14 asthmatic patients with normal pulmonary function, 14 patients with COA, 11 patients in the Asthma AE group, and 14 healthy subjects. Isolated circulating fibrocytes were used for migration assay. Expression of CCR7, CXCR4, S100A9, and RAGE in fibrocytes was measured by using flow cytometry. CCL19 and CXCL12 expression in bronchial tissues was determined by using immunohistochemistry and RT-PCR.
  
  
  RESULTS
  There were higher numbers of circulating fibrocytes in patients in the Asthma AE group and patients with COA. The expression of CXCL12 in bronchial tissues and CXCR4 in circulating fibrocytes was higher in the Asthma AE group and, to a lesser extent, in patients with COA. The expression of CCL19 in bronchial tissues and CCR7 in fibrocytes was higher in patients with COA. CXCL12/CXCR4 and CCL19/CCR7 enhanced fibrocyte transmigration in the Asthma AE group and in patients with COA, respectively. The upregulated expression of S100A9 and RAGE in fibrocytes of patients in the Asthma AE group and those with COA contributes to the enhanced basal migratory motility of fibrocytes.
  
  
  CONCLUSIONS
  The CXCR4/CXCL12 axis contributes to chemotaxis of fibrocytes in patients in the Asthma AE group, whereas the CCR7/CCL19 axis plays an important role in patients with COA. S100A9 enhances the basal migratory motility of fibrocytes from patients in the Asthma AE group and patients with COA.
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Institute of NanoEngineering and MicroSystems, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Tushar Harishchandra
authors.initials: TH
authors.lastname: Punde
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Chien-Da
authors.initials: CD
authors.lastname: Huang
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Pai-Chien
authors.initials: PC
authors.lastname: Chou
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Tzu-Ting
authors.initials: TT
authors.lastname: Huang
authors.affiliation: Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Wu
authors.affiliation: Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Liu
authors.affiliation: National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: q8828@ms11.hinet.net.
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D001249:Asthma / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D040502:Calgranulin B / Q000378:metabolism; D016022:Case-Control Studies; D002465:Cell Movement / Q000235:genetics; D054415:Chemokine CCL19 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology
chemical_list: D040502:Calgranulin B; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D054400:Receptors, CCR7; D019718:Receptors, CXCR4
keywords: Asthma; S100A9; chemokine receptors; chemokines; fibrocytes