Glomerular endothelium exhibits enhanced expression of costimulatory adhesion molecules, CD80 and CD86, by warm ischemia/reperfusion injury in rats.
Recent studies suggested that the vascular endothelial cells function as a resident antigen-presenting cell (APC) in certain situations such as organ transplantation, and the ischemia/reperfusion injury, an inevitable event in organ transplantation, leads to an enhanced biosynthesis of cell adhesion molecules. We have demonstrated that the hepatic sinusoidal endothelial cells have potential ability as APCs by expressing the costimulatory adhesion molecule proteins, CD80 (B7-1) and CD86 (B7-2), of which expression was enhanced by warm ischemia/reperfusion of the rat liver. In this study, we assessed the localization of CD80, CD86, and intercellular adhesion molecule 1 in the rat kidneys and the influence of warm ischemia/reperfusion with or without a hypercreatinemic condition on the expression of these adhesion molecules in the renal tissues. Wistar male rats weighing 150 to 230 g were divided into group A, receiving a sham-operation (control), group B, receiving 1-hour clamping of the left renal pedicle (temporary ischemia), and group C, receiving right nephrectomy and 1-hour clamping of the left renal pedicle (temporary ischemia with hypercreatinemia). The left kidneys were submitted to immunohistochemical and molecular analyses sequentially for the period of 14 days. We found that CD80, CD86, and intercellular adhesion molecule 1 proteins localized on the glomerular and peritubular endothelium and were up-regulated after ischemia/reperfusion. The up-regulation of these three proteins was enhanced by the hypercreatinemic condition. The relative mRNA levels analyzed by real-time reverse transcription polymerase chain reaction showed that CD80 and CD86 expressions were constitutively observed and significantly increased for 14 days after the warm ischemia reperfusion with a peak level at Day 3 (6.7- and 20.8-fold increase for CD80 and CD86, respectively). Our results suggested that the glomerular endothelial cells will play a pivotal role as a APC by expressing CD80 and CD86 in the induction of renal tissue injury associated with the ischemia/reperfusion at renal transplantation surgery, as well as the peritubular endothelium.
Satoh
Shigeru
S
Department of Urology, Akita University School of Medicine, Akita, Japan.
Suzuki
Akira
A
Asari
Yasushi
Y
Sato
Mitsuru
M
Kojima
Naosuke
N
Sato
Takeya
T
Tsuchiya
Norihiko
N
Sato
Kazunari
K
Senoo
Haruki
H
Kato
Tetsuro
T
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics; D018122:B7-1 Antigen / Q000032:analysis* / Q000235:genetics; D051940:B7-2 Antigen; D003404:Creatinine / Q000097:blood; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D007511:Ischemia / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D003404:Creatinine