Apoptosis and cellular activation in the pathogenesis of acute vascular rejection.
Acute vascular or humoral rejection, a vexing outcome of organ transplantation, has been attributed by some to activation and by others to apoptosis of endothelial cells in the graft. We asked which of these processes causes acute vascular rejection by tracing the processes during the development of acute vascular rejection in porcine cardiac xenografts performed in baboons. Apoptosis, assayed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), expression of activated caspase-3, and proapoptotic genes Bax and Bcl-x(L), was not detected until acute vascular rejection was well advanced, and even then, apoptosis was largely confined to myocytes. Activation of the endothelium, as evidenced by expansion of rough endoplasmic reticulum and increased ribosomal antigen and phospho-p70 S6 kinase, occurred early in the course of acute vascular rejection and progressed through the disease process. These findings suggest that acute vascular rejection is caused by an active metabolic process and not by apoptosis in the endothelium.
Holzknecht
Zoie E
ZE
Department of Surgery, Mayo Clinic, Rochester, Minn 55905, USA.
Kuypers
Karisha L
KL
Plummer
Timothy B
TB
Williams
Josie
J
Bustos
Matilda
M
Gores
Gregory J
GJ
Brunn
Gregory J
GJ
Platt
Jeffrey L
JL
D000208:Acute Disease; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001808:Blood Vessels / Q000276:immunology* / Q000473:pathology; D018957:CD59 Antigens / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005337:Fibrin / Q000378:metabolism; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006168:Guinea Pigs; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D010215:Papio; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000276:immunology
D018957:CD59 Antigens; D005337:Fibrin