Expression of IL-8 during reperfusion of renal allografts is dependent on ischemic time.
BACKGROUND
Ischemia/reperfusion injury is an inherent consequence of solid organ transplantation that increases tissue inflammation and negatively impacts organ transplant function and survival. This study investigated the expression levels of chemokine and chemokine receptor genes in living versus cadaver donor renal allografts before and after reperfusion.


METHODS
This study involved 39 renal transplant patients (19 cadaveric and 20 living donor). The ischemia biopsy was taken just before graft declamping and the reperfusion biopsy 30 min after declamping. Whole-cell RNA was isolated and chemokine (IL-8, CCL2/MCP-1, CXCL10/IP-10 and CCL5/RANTES) and chemokine receptor (CCR2 and CCR5) expression was tested by quantitative PCR.


RESULTS
Just prior to declamping, ischemic cadaveric donor grafts had higher expression of CXCL10/IP-10 but not IL-8 or CCL2/MCP-1 than living donor grafts. IL-8 expression increased 50% from ischemia to reperfusion in living donor grafts but increased more than 13-fold during reperfusion of cadaver donor grafts. Increased total ischemia time induced greater IL-8 expression during reperfusion. MCP-1 expression also increased during reperfusion of living and cadaver donor grafts but differences were not observed between the two groups of grafts. RANTES, CCR2, and CCR5 expression did not change in ischemic vs. reperfusion biopsies.


CONCLUSIONS
The expression of chemokines directing neutrophil and macrophage recruitment increases during reperfusion of living and cadaveric donor renal allografts. Expression levels of IL-8 correlate with the ischemic time imposed on the renal graft. Early tissue injury may be attenuated by strategies antagonizing chemokines directing the recruitment of neutrophils and macrophages into kidney grafts.
Araki
Motoo
M
Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Fahmy
Nader
N
Zhou
Lingmei
L
Kumon
Hiromi
H
Krishnamurthi
Venkatesh
V
Goldfarb
David
D
Modlin
Charles
C
Flechner
Stuart
S
Novick
Andrew C
AC
Fairchild
Robert L
RL
D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D050377:Cold Ischemia; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D015424:Reperfusion; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology*; D014019:Tissue Donors
C111835:CCL2 protein, human; C515334:CCR2 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016209:Interleukin-8; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine