title: Met-RANTES ameliorates fibrous airway obliteration and decreases ERK expression in a murine model of bronchiolitis obliterans.
abstract: OBJECTIVE
  Bronchiolitis obliterans (BO) is the main cause of late mortality among long-term survivors of lung transplantation. Chemokine-chemokine receptor (CCR) interaction and subsequent recruitment of infiltrating cells to the graft are early events in the development of chronic rejection of transplanted lungs. The present study investigated whether blockade of chemokine receptors CCR1 and CCR5 with Met-regulated-on-activation, normal T cells expressed and secreted (RANTES), an amino-terminal modified derivative of RANTES/CCL5, affects the development of BO in murine model and we sought to determine the expression of RANTES/CCL5 and their relationship with extracellular signal-regulated kinase (ERK).
  
  
  METHODS
  BALB/c mouse tracheas were heterotopically transplanted into C57Black6 recipients and treated for 21 days with either Met-RANTES at 20 microg/day or vehicle. Animals were killed at 21 days after transplantation for histologic examination of ERK expression.
  
  
  RESULTS
  RANTES/CCL5 was highly expressed in allografts compare to isografts. Met-RANTES treatment ameliorated fibrous airway obliteration in a mouse model of BO and decreased ERK expression.
  
  
  CONCLUSIONS
  Blockade of chemokine receptors by Met-RANTES ameliorated airway obliteration and decreased ERK expression. These findings suggest that chemokine receptors CCR1 and CCR5 play significant roles in the development of chronic rejection and ERK may be a new molecular target for chronic rejection.
authors.affiliation: Department of Thoracic Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Uchida
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kajiwara
authors.forename: Aeru
authors.initials: A
authors.lastname: Hayashi
authors.forename: Kuniharu
authors.initials: K
authors.lastname: Miyajima
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nagatsuka
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Taira
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kimura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuboi
authors.forename: Harubumi
authors.initials: H
authors.lastname: Kato
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001989:Bronchiolitis Obliterans / Q000378:metabolism / Q000503:physiopathology*; D018946:Chemokine CCL5; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006084:Graft Rejection / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000502:physiology*; D019707:Receptors, Chemokine / Q000502:physiology*; D014132:Trachea / Q000637:transplantation*; D014183:Transplantation, Heterologous
chemical_list: C515301:Ccr1 protein, mouse; D018946:Chemokine CCL5; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D048049:Extracellular Signal-Regulated MAP Kinases