Correlation of Fas and Fas ligand expression with rejection status of transplanted heart in human.
BACKGROUND
Activation of pro-apoptotic systems has been proven in rejection model of animal heart transplantation. The role of Fas and Fas ligand (FasL) in graft rejection is not fully understood, and the expression changes of these genes in human transplanted heart have not been elucidated.


METHODS
Endomyocardial biopsy samples were taken from 13 consecutive patients undergoing heart transplantation at various times, and they were classified into rejection (REJ, grade 3A or more) and lack of rejection (TOL, grade 1B or less) by International Society of Heart and Lung Transplantation rejection grade. Semiquantitative reverse transcription-polymerase chain reaction and immunohistochemistry were performed to evaluate the status of Fas and FasL expression in each sample.


RESULTS
Fas was constitutively expressed both in REJ and TOL specimens (expression levels normalized by glyceraldehyde-3-phosphate dehydrogenase expression in semiquantitative reverse transcription-polymerase chain reaction of REJ vs. TOL, 0.842+/-0.096 vs. 0.848+/-0.103, P=0.776); however, FasL expression was detected in 66% of REJ samples and 40% of TOL samples. Normalized levels of FasL expression were 0.591+/-0.494 (REJ) and 0.383+/-0.507 (TOL) (P<0.05). FasL was expressed by cardiomyocytes as well as graft-infiltrating cells.


CONCLUSIONS
This up-regulation of FasL may be one of possible mechanisms of apoptosis in rejection process of human cardiac allograft.
Oh
S I
SI
Heart Research Institute, Department of Internal Medicine, Seoul National University College of Medicine, Korea.
Kim
I W
IW
Jung
H C
HC
Seo
J W
JW
Chae
I H
IH
Kim
H S
HS
Oh
B H
BH
D000328:Adult; D001706:Biopsy; D004699:Endocardium / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006085:Graft Survival; D006321:Heart / Q000503:physiopathology; D016027:Heart Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor