title: Inhibition of allergic bronchial asthma by thrombomodulin is mediated by dendritic cells.
abstract: BACKGROUND
  bronchial asthma is caused by inappropriate acquired immune responses to environmental allergens. It is a major health problem, with a prevalence that is rapidly increasing. Curative therapy is not currently available.
  
  
  OBJECTIVE
  to test the hypothesis that thrombomodulin (TM) inhibits allergic bronchial asthma by inducing tolerogenic dendritic cells (DCs).
  
  
  METHODS
  the protective effect of TM was evaluated using a murine asthma model. Asthma was induced in mice by exposure to chicken egg ovalbumin, and the effects of inhaled TM or TM-treated DCs were assessed by administering before ovalbumin exposure.
  
  
  RESULTS
  treatment with TM protects against bronchial asthma measured as improved lung function and reduced IgE and cells in alveolar lavage fluid by inducing tolerogenic dendritic dells. These are characterized by high expression of surface TM (CD141/TM(+)) and low expression of maturation markers and possess reduced T-cell costimulatory activity. The CD141/TM(+) DCs migrate less toward chemokines, and after TM treatment there are fewer DCs in the draining lymph node and more in the lungs. The TM effect is independent of its role in coagulation. Rather, it is mediated via the TM lectin domain directly interacting with the DCs.
  
  
  CONCLUSIONS
  the results of this study show that TM is a modulator of DC immunostimulatory properties and a novel candidate drug for the prevention of bronchial asthma in atopic patients.
authors: Department of Immunology, Mie University School of Medicine, Edobashi 2-174, Tsu City, Mie Prefecture 514 8507, Japan.
authors: Takehiro
authors: T
authors: Takagi
authors: Osamu
authors: O
authors: Taguchi
authors: Masaaki
authors: M
authors: Toda
authors: Daniel Boveda
authors: DB
authors: Ruiz
authors: Paloma Gil
authors: PG
authors: Bernabe
authors: Corina N
authors: CN
authors: D'Alessandro-Gabazza
authors: Yasushi
authors: Y
authors: Miyake
authors: Tetsu
authors: T
authors: Kobayashi
authors: Shinya
authors: S
authors: Aoki
authors: Fumiko
authors: F
authors: Chiba
authors: Yutaka
authors: Y
authors: Yano
authors: Edward M
authors: EM
authors: Conway
authors: Seiichi
authors: S
authors: Munesue
authors: Yasuhiko
authors: Y
authors: Yamamoto
authors: Hiroshi
authors: H
authors: Yamamoto
authors: Koji
authors: K
authors: Suzuki
authors: Yoshiyuki
authors: Y
authors: Takei
authors: John
authors: J
authors: Morser
authors: Esteban C
authors: EC
authors: Gabazza
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D051379:Mice; D011994:Recombinant Proteins; D018180:Thrombomodulin / Q000008:administration & dosage*
chemical_list: D011994:Recombinant Proteins; D018180:Thrombomodulin