Jose, MD and Ikezumi, Y and Van Rooijen, N and Atkins, RC and Chadban, SJ, Macrophages act as effectors of tissue damage in acute renal allograft rejection, Transplantation, 76, (7) pp. 1015-22. ISSN 0041-1337 (2003) [Refereed Article]
Copyright 2003 Lippincott Williams & Wilkins
BACKGROUND: Macrophages constitute 38% to 60% of infiltrating cells during acute renal allograft rejection. Their contribution to tissue damage during acute rejection was examined by depleting macrophages in a rat model.
METHODS: Lewis rats underwent bilateral nephrectomy and then received a Dark Agouti renal allograft and liposomal-clodronate, control phosphate-buffered saline liposomes, or saline intravenously (n=7 per group) on days 1 and 3 postsurgery. Grafts were harvested on day 5.
RESULTS: Liposomal-clodronate treatment resulted in a 70% reduction in blood ED1+ monocytes and 60% reduction in intragraft ED1+ macrophages (both P<0.01). Half of all remaining interstitial ED1+ cells were undergoing apoptosis (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling+/ED1+), and thus functional depletion of more than 75% of macrophages was achieved. Histologic and functional parameters of acute rejection were attenuated: interstitial infiltrate, tubulitis, and glomerulitis (P<0.01); tubular cell apoptosis (P<0.001); tubular cell proliferation (P<0.001); and serum creatinine (P<0.01). Production of inducible nitric oxide synthase by infiltrating cells and urinary nitric oxide excretion was reduced by 90% (P<0.001). In contrast, no reduction in the number of other leukocytes was seen (CD3+, CD4+, CD8+, and natural killer cells). Activation of lymphocytes (CD25+) and production of lymphocyte effector molecules (granzyme B) were unaltered.
CONCLUSION: This study demonstrates that macrophages contribute to tissue damage during acute rejection.
|Item Type:||Refereed Article|
|Research Division:||Medical and Health Sciences|
|Research Group:||Clinical Sciences|
|Research Field:||Nephrology and Urology|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Urogenital System and Disorders|
|UTAS Author:||Jose, MD (Professor Matthew Jose)|
|Web of Science® Times Cited:||93|
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