title: Adenovirus mediated IL-10 gene transfer to the airway of the rat lung for prevention of lung allograft rejection.
abstract: BACKGROUND
  The ability to express genes with potential immunoregulatory capacity could reduce allograft rejection (AR). We examined the feasibility of transferring the viral interleukin-10 (vIL-10) gene into rat lungs by intra-bronchial instillation and the subsequent effects of delivered vIL-10 on acute lung AR.
  
  
  METHODS
  First, the adenoviral beta-galactosidase vector (adv-beta-gal) particles were instilled into the airway of the rat lung and protein synthesis of beta-gal was examined by histochemical staining. Next, the ability of the adenoviral vIL-10 vector (adv-vIL-10) transfection to modify AR was examined in a highly histoincompatible rat lung transplant model (BN-->Lew). Donor left lungs were transfected with 3 x 10(8) pfu/0.3 mL of adv-vIL-10 (vIL-10 group) or adv-beta-gal (control group) 3 days before transplantation. On day 6 post-transplant, lung allografts were harvested and AR was graded histologically (stage 0-4). Several pathological categories of inflammation (perivascular, peribronchial, or peribronchiolar mononuclear infiltrates, edema, vasculitis, intraalveolar hemorrhage, and necrosis) were also examined and scored on a scale of 0-4 as previously described.
  
  
  RESULTS
  A successful transgene protein synthesis by adv-beta-gal in alveolar epithelial cells and alveolar macrophages was confirmed by histochemical staining with X-gal. The vIL-10 group showed a trend toward an improved stage of AR (3.75 +/- 0.5 vs. 4.0 +/- 0), and also a decreased pathological scores for edema (3.5 +/- 0.6 vs. 4.0 +/- 0), intraalveolar hemorrhage (2.3 +/- 1.0 vs. 2.5 +/- 0.6) and necrosis (1.5 +/- 0.5 vs. 1.75 +/- 1.3) compared with the control group, however, the differences in any pathological scores between the two groups did not reach a statistical significance.
  
  
  CONCLUSIONS
  1. A successful transgene protein synthesis in alveolar epithelial cells was ensured by intra-bronchial instillation of an adenoviral vector encoding beta-galactosidase gene. 2. Transferring the vIL-10 gene into rat lungs by intra-bronchial instillation did not seem to reduce lung AR significantly, as opposed to the results of our previous experiments in a rat cardiac allograft model. This discrepancy may be explained by several potential factors including the immunogenecity of adenoviral vectors in conjunction with the nature of the lung more susceptible to immune response and inflammation.
authors.affiliation: Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan. yokada@idac.tohoku.ac.jp
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Okada
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Zuo
authors.forename: Mieko
authors.initials: M
authors.lastname: Toyoda
authors.forename: Alberto
authors.initials: A
authors.lastname: Marchevsky
authors.forename: Jack M
authors.initials: JM
authors.lastname: Matloff
authors.forename: Hisashi
authors.initials: H
authors.lastname: Oishi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Jordan
mesh_terms: D000256:Adenoviridae; D000818:Animals; D015316:Genetic Therapy; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D011650:Pulmonary Alveoli / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014161:Transduction, Genetic; D014184:Transplantation, Homologous
chemical_list: D016753:Interleukin-10