Increased expression of endoarterial vascular cell adhesion molecule-1 mRNA in an experimental model of lung transplant rejection: diagnosis by pulmonary arterial biopsy.
BACKGROUND
Early detection of rejection after lung transplantation may prevent allograft failure. This study determines if mRNA from the cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in pulmonary endovascular tissue samples could be markers of early rejection.


METHODS
Single left lung transplants were performed in five dogs. Each dog was treated for 2 weeks with immunosuppression, after which rejection was allowed to occur. Percutaneous biopsies from 2- to 3-mm distal branch pulmonary arteries were obtained in each dog from the normal and the transplanted lungs at the end of immunosuppression therapy and periodically (2-4 times) for 1 to 3 weeks until euthanasia. Levels of cell adhesion molecule mRNA in the biopsy samples were quantitated by reverse-transcriptase polymerase chain reaction and normalized to beta-actin mRNA levels.


RESULTS
Between three and five pulmonary endoarterial biopsy samples were obtained from each lung at each catheterization procedure. There was a significant increase in VCAM-1 mRNA levels in the biopsies of the transplanted lungs (which were undergoing rejection) compared with the native right lungs in all dogs. Progressive increases in VCAM-1 mRNA were observed with longer rejection times. VCAM-1 mRNA changes were detected earlier than histologic changes of rejection.


CONCLUSIONS
In pulmonary endoarterial biopsy samples obtained in a canine lung transplant model, there was a progressive increase in VCAM-1 mRNA levels with increasing rejection. Changes in VCAM-1 mRNA were observed earlier than histologic changes of rejection. VCAM-1 quantitation by endoarterial biopsy may be useful in surveillance and early diagnosis of rejection in patients who undergo lung transplantation.
Rothman
Abraham
A
Division of Cardiology, Department of Pediatrics, University of California-San Diego, Children's Hospital San Diego, 3020 Children's Way, 5004, San Diego, CA 92123. arothman@chsd.org
Mann
David
D
Behling
Cynthia A
CA
McGraw
Melanie
M
Seslar
Steven
S
Shiu
Perkin
P
Zhang
Lingzhi
L
Kriett
Jolene M
JM
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D004285:Dogs; D019040:E-Selectin / Q000235:genetics; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016040:Lung Transplantation; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D019040:E-Selectin; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1