Role of adhesion molecules and dendritic cells in rat hepatic/renal ischemia-reperfusion injury and anti-adhesive intervention with anti-P-selectin lectin-EGF domain monoclonal antibody.
OBJECTIVE
To investigate the role of P-selectin, intercellular adhesion molecule-1 (ICAM-1) and dendritic cells (DCs) in liver/kidney of rats with hepatic/renal ischemia-reperfusion injury and the preventive effect of anti-P-selectin lectin-EGF domain monoclonal antibody (anti-PsL-EGFmAb) on the injury.


METHODS
Rat models of hepatic and renal ischemia-reperfusion were established. The rats were then divided into two groups, one group treated with anti-PsL-EGFmAb (n = 20) and control treated with saline (n = 20). Both groups were subdivided into four groups according to reperfusion time (1, 3, 6 and 24 h). The sham-operated group (n = 5) served as a control group. DCs were observed by the microscopic image method, while P-selectin and ICAM-1 were analyzed by immunohistochemistry.


RESULTS
P-selectin increased significantly in hepatic sinusoidal endothelial cells and renal tubular epithelial cells 1 h after ischemia-reperfusion, and the expression of ICAM-1 was up-regulated in hepatic sinusoid and renal vessels after 6 h. CD1a(+)CD80(+)DCs gradually increased in hepatic sinusoidal endothelium and renal tubules and interstitium 1 h after ischemia-reperfusion, and there was the most number of DCs in 24-h group. The localization of DCs was associated with rat hepatic/renal function. These changes became less significant in rats treated with anti-PsL-EGFmAb.


CONCLUSIONS
DCs play an important role in immune pathogenesis of hepatic/renal ischemia-reperfusion injury. Anti-PsL-EGFmAb may regulate and inhibit local DC immigration and accumulation in liver/kidney.
Zhou
Tong
T
Department of Nephrology, Rui Jin Hospital, Shanghai Second Medical University, Shanghai 200025, China. zhoutong_cn@hotmail.com
Sun
Gui-Zhi
GZ
Zhang
Ming-Jun
MJ
Chen
Jin-Lian
JL
Zhang
Dong-Qing
DQ
Hu
Qing-Shen
QS
Chen
Yu-Ying
YY
Chen
Nan
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000276:immunology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007668:Kidney / Q000473:pathology; D037102:Lectins; D008099:Liver / Q000473:pathology; D008297:Male; D019007:P-Selectin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
D000911:Antibodies, Monoclonal; D037102:Lectins; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D004815:Epidermal Growth Factor
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