Role of platelet-derived growth factor in obliterative bronchiolitis (chronic rejection) in the rat

The role of platelet-derived growth factor (PDGF) in the development of obliterative bronchiolitis (OB) as a manifestation of chronic rejection was investigated in the heterotopic rat tracheal allograft model. An increase in intragraft PDGF-Ralpha and -Rbeta mRNA expression, and in PDGF-AA and -Ralp...

Full description

Saved in:
Bibliographic Details
Published in:American journal of respiratory and critical care medicine 1999-10, Vol.160 (4), p.1324-1332
Main Authors: KALLIO, E. A, KOSKINEN, P. K, AAVIK, E, BUCHDUNGER, E, LEMSTRÖM, K. B
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bronchiolitis Obliterans - metabolism
Bronchiolitis Obliterans - pathology
Bronchiolitis Obliterans - physiopathology
Cell Division - drug effects
Chronic Disease
Cyclosporine - pharmacology
Enzyme Inhibitors - pharmacology
Graft Rejection - metabolism
Graft Rejection - pathology
Graft Rejection - physiopathology
Immunohistochemistry
Immunosuppressive Agents - pharmacology
Male
Medical sciences
Platelet-Derived Growth Factor - physiology
Polymerase Chain Reaction
Protein-Tyrosine Kinases - antagonists & inhibitors
Pyridines - pharmacology
Pyrimidines - pharmacology
Rats
Rats, Inbred Strains
Receptor, Platelet-Derived Growth Factor alpha - metabolism
Receptor, Platelet-Derived Growth Factor beta - metabolism
Respiratory Mucosa - pathology
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the respiratory system
Trachea - metabolism
Trachea - pathology
Trachea - transplantation
Transplantation, Homologous
Transplantation, Isogeneic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The role of platelet-derived growth factor (PDGF) in the development of obliterative bronchiolitis (OB) as a manifestation of chronic rejection was investigated in the heterotopic rat tracheal allograft model. An increase in intragraft PDGF-Ralpha and -Rbeta mRNA expression, and in PDGF-AA and -Ralpha immunoreactivity, was demonstrated during the progressive loss of respiratory epithelium and airway occlusion in nontreated allografts compared with syngeneic grafts. Treatment with CGP 53716, a protein-tyrosine kinase inhibitor selective for PDGF receptor, alone and in combination with suboptimal doses of cyclosporin A, significantly reduced myofibroproliferation and the degree of OB by more than 50%. CGP 53716 did not affect airway wall inflammatory cell proliferation, the number of graft-infiltrating CD4(+) or CD8(+) T cells, ED3(+) macrophages, or the level of immune activation determined as IL-2R and MHC class II expression. This study suggests a regulatory role for PDGF, especially for PDGF-AA and -Ralpha, in the development of obliterative bronchiolitis in this model, and demonstrates that inhibition of PDGF receptor protein-tyrosine kinase activation prevents these obliterative changes. Thus, receptor protein-tyrosine kinase inhibitors may provide a novel therapeutic strategy for the prevention of chronic rejection.
ISSN:1073-449X
1535-4970
DOI:10.1164/ajrccm.160.4.9802006