PMID- 10616213
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20061115
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 79
IP  - 12
DP  - 1999 Dec
TI  - Bax and apoptosis in acute and chronic rejection of rat cardiac allografts.
PG  - 1643-53
AB  - Apoptosis is associated with acute rejection, transplant vascular disease, and 
      the "Quilty effect" in cardiac allografts. However, the causality and mechanisms 
      of apoptosis in the pathogenesis of vascular injury are poorly understood. In the 
      current study, the Lewis-to-F344 rat cardiac allograft model was utilized as a 
      means to immunohistochemically evaluate the expression of Bax, Bcl-2, and factor 
      VIII-related antigen in transplant vascular disease. Apoptosis was detected by in 
      situ labeling of fragmented DNA using in situ terminal deoxyribonucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) in native hearts and grafted 
      hearts of allogeneic and syngeneic recipients. Bax immunostaining was detected in 
      50% of endothelial cells, in 60% of infiltrating leukocytes associated with acute 
      rejection in the myocardium, and in certain other parenchymal cells, considering 
      all cardiac allografts. More than 75% of infiltrating leukocytes in the intima of 
      vessel walls immunostained positive for Bax. Bcl-2 immunopositivity was not 
      detected in native hearts, allo allo-, or syngrafts. On Days 2, 4, 7, and 14 
      after transplantation, TUNEL positivity was detected in only about 1% of 
      leukocytes in the interstitial infiltrates, despite the fact that rather severe 
      rejection was observed in Day 14 allografts. The number of apoptotic leukocytes 
      increased significantly by Days 28 and 56 after transplantation, although the 
      severity of histopathological rejection did not increase as compared with Day 14. 
      The apoptotic leukocytes remained isolated or in small clusters, mainly 
      perivascular. TUNEL positivity colocalized with Bax expression in these cells. 
      TUNEL staining was also observed in certain parenchymal cells in the interstitium 
      and in randomly distributed inflammatory cells in vessel walls. TUNEL positivity 
      was detected in rare luminal endothelial cells in transverse sections of vessel 
      walls (about 10% of cells in <1/10 of the vessels studied). Nuclear TUNEL 
      positivity was observed in Bax-negative cardiomyocytes in ischemically damaged 
      areas of myocardium in both allografts and syngrafts. In summary, increased 
      expression of Bax was observed in rat cardiac allografts. The colocalization of 
      TUNEL and Bax suggests that endothelial cell injury and infiltrating leukocyte 
      apoptosis may be regulated in part by the apoptosis-promoting protein, Bax. In 
      the current model, myocyte death due to ischemia and surgical injury in syngrafts 
      and allografts does not seem to involve Bax.
FAU - Dong, C
AU  - Dong C
AD  - Department of Pathology and Laboratory Medicine, St. Paul's Hospital-University 
      of British Columbia, Vancouver, Canada.
FAU - Granville, D J
AU  - Granville DJ
FAU - Tuffnel, C E
AU  - Tuffnel CE
FAU - Kenyon, J
AU  - Kenyon J
FAU - English, D
AU  - English D
FAU - Wilson, J E
AU  - Wilson JE
FAU - McManus, B M
AU  - McManus BM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Bax protein, rat)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - *Graft Rejection
MH  - *Heart Transplantation
MH  - Immunohistochemistry
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Proto-Oncogene Proteins/metabolism/*physiology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism/physiology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Inbred Lew
MH  - Transplantation, Homologous
MH  - bcl-2-Associated X Protein
EDAT- 2000/01/01 00:00
MHDA- 2000/01/01 00:01
CRDT- 2000/01/01 00:00
PHST- 2000/01/01 00:00 [pubmed]
PHST- 2000/01/01 00:01 [medline]
PHST- 2000/01/01 00:00 [entrez]
PST - ppublish
SO  - Lab Invest. 1999 Dec;79(12):1643-53.