TY - JOUR
T1 - The effect of murine anti-thymocyte globulin on experimental kidney warm ischemia-reperfusion injury in mice
AU - Jang, Hye Ryoun
AU - Gandolfo, Maria Teresa
AU - Ko, Gang Jee
AU - Racusen, Lorraine
AU - Rabb, Hamid
N1 - Funding Information:
We thank Chaitali Sarkar and Priya Kesari for technical assistance. This study was supported by the Genzyme Corp. HR is supported by the US National Institutes of Health, US National Kidney Foundation, and Talecris Biotech.Inc, grants. HRJ was supported by Korea Research Foundation.
PY - 2009/1
Y1 - 2009/1
N2 - Kidney ischemia-reperfusion injury (IRI) is an important contributor to delayed graft function (DGF) and poor outcome of allografts. Small clinical studies suggest a beneficial role for human anti-thymocyte globulin (ATG) in DGF. We investigated the short-term effect of mouse anti-thymocyte globulin (mATG) on kidney warm IRI in mice. We administered either mATG, rabbit immunoglobulin (RIgG), or saline with different dosing schedules in three different IRI models: 30 min bilateral, 60 min bilateral, and 45 min unilateral IRI. mATG effectively depleted circulating T cells but had less effect on kidney-infiltrating T cells. There was no difference in serum creatinine levels between groups in each study. Scoring of renal tubular damage and regenerating tubules revealed no difference between groups. The percentage of CD3+CD4-CD8- double-negative (DN) T cells, which were reported to contribute to the pathogenesis of lupus nephritis, increased and the percentages of regulatory T cells and NK cells decreased in the post-ischemic kidneys of mATG treated mice. mATG did not alter the expression of pro-inflammatory cytokines such as IFN-γ or anti-inflammatory cytokines such as IL-10 in post-ischemic kidneys. mATG treatment, whether initiated before ischemia or immediately after reperfusion, had minimal effects on renal injury following warm IRI in mice.
AB - Kidney ischemia-reperfusion injury (IRI) is an important contributor to delayed graft function (DGF) and poor outcome of allografts. Small clinical studies suggest a beneficial role for human anti-thymocyte globulin (ATG) in DGF. We investigated the short-term effect of mouse anti-thymocyte globulin (mATG) on kidney warm IRI in mice. We administered either mATG, rabbit immunoglobulin (RIgG), or saline with different dosing schedules in three different IRI models: 30 min bilateral, 60 min bilateral, and 45 min unilateral IRI. mATG effectively depleted circulating T cells but had less effect on kidney-infiltrating T cells. There was no difference in serum creatinine levels between groups in each study. Scoring of renal tubular damage and regenerating tubules revealed no difference between groups. The percentage of CD3+CD4-CD8- double-negative (DN) T cells, which were reported to contribute to the pathogenesis of lupus nephritis, increased and the percentages of regulatory T cells and NK cells decreased in the post-ischemic kidneys of mATG treated mice. mATG did not alter the expression of pro-inflammatory cytokines such as IFN-γ or anti-inflammatory cytokines such as IL-10 in post-ischemic kidneys. mATG treatment, whether initiated before ischemia or immediately after reperfusion, had minimal effects on renal injury following warm IRI in mice.
KW - Anti-thymocyte globulin
KW - Immune mechanisms
KW - Ischemia-reperfusion injury
UR - http://www.scopus.com/inward/record.url?scp=70449525197&partnerID=8YFLogxK
U2 - 10.1016/j.trim.2009.08.001
DO - 10.1016/j.trim.2009.08.001
M3 - Article
C2 - 19682579
AN - SCOPUS:70449525197
SN - 0966-3274
VL - 22
SP - 44
EP - 54
JO - Transplant Immunology
JF - Transplant Immunology
IS - 1-2
ER -