Analysis of Fas system in pulmonary injury of graft-versus-host disease after rat intestinal transplantation

The lung is one of the primary targets of acute graft-versus-host disease ( GVHD), which is the principal complication that occurs after allogeneic int estinal transplantation. The purpose of this study is to investigate the in volvement of Fas/Fas ligand system in pulmonary injury after rat semi-allog eneic intestinal transplantation. The lungs mere serially harvested from LE W x BN F1(LBNF1) recipients of either LEW heterotopic intestinal allografts or LBNF1 isografts, on days 1, 3, 5, 9, and 13 posttransplant. In light mi croscopy, pulmonary injury became apparent on day 13 in the allogeneic comb ination, showing a thickening of the alveolar septa, The incidence of apopt osis, examined by terminal deoxynucleotidyl transferase-mediated deoxyuridi ne triphosphate (dUTP) biotin nick end-labeling, was observed to increase s teadily in the alveolar cells accompanied by a progression of GVHD, In an i mmunohistochemical study, Fas was constitutively expressed in the lung, alt hough Fas ligand was expressed most extensively on day 9, The immunoreactiv ity of both Fas and Fas ligand mere observed in alveolar cells, in addition to leukocytes, An analysis by reverse transcription polymerase chain react ion also revealed that the expression of Fas mRNA mas constitutive without any significant change, although that of Fas ligand mRNA increased substant ially and peaked on day 9, which was significant compared to the isogeneic combination. In conclusion, transcriptionally up-regulated Fas ligand and i ncreased number of apoptosis suggests that the Fas system may play a role i n the pathophysiology of GVHD-induced pulmonary injury.