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Macrophages act as effectors of tissue damage in acute renal allograft rejection


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 Statement

Copyright 2003 Lippincott Williams & Wilkins

DOI: doi:10.1097/01.TP.0000083507.67995.13


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 Details

Item Type:Refereed Article
Keywords:allograft rejection
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Nephrology and urology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Jose, MD (Professor Matthew Jose)
ID Code:90571
Year Published:2003
Web of Science® Times Cited:102
Deposited By:Medicine
Deposited On:2014-04-10
Last Modified:2016-11-17

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