Platelet-derived growth factor regulates cytomegalovirus infection-enhanced obliterative bronchiolitis in rat tracheal allografts.
BACKGROUND
Cytomegalovirus (CMV) infection is a risk factor for the development of obliterative bronchiolitis (OB) after lung transplantation.


METHODS
In the rat tracheal allograft model, rat CMV (RCMV) infection is associated with accelerated OB through enhanced alloimmune activation and increased smooth muscle cell (SMC) proliferation. Using this model, we investigated the role of platelet-derived growth factor (PDGF) in RCMV infection-enhanced OB.


RESULTS
Immunohistochemistry and in situ hybridization revealed that RCMV infection significantly up-regulates PDGF ligand and receptor expression in inflammatory and SMC-like cells in tracheal allografts. Selective inhibition of PDGF receptor tyrosine kinase activity by CGP 53716 prevents the development of OB in RCMV-infected allograft recipients.


CONCLUSIONS
The results of this study emphasize the key regulatory role of PDGF in the pathogenesis of RCMV infection-enhanced OB, suggesting a novel strategy for the prevention of this fibroproliferative disorder.
Tikkanen
Jussi M
JM
Cardiopulmonary Research Group, Transplantation Laboratory, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. jussi.tikkanen@helsinki.fi
Krebs
Rainer
R
Bruggeman
Cathrien
C
Lemström
Karl B
KB
Koskinen
Petri K
PK
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D008024:Ligands; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000637:transplantation*; D014184:Transplantation, Homologous
C092972:CGP 53716; D008024:Ligands; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines; D011743:Pyrimidines; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; C095477:platelet-derived growth factor AB; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor