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Blockade of macrophage colony-stimulating factor reduces macrophage proliferation and accumulation in renal allograft rejection


Jose, MD and Le Meur, Y and Atkins, RC and Chadban, SJ, Blockade of macrophage colony-stimulating factor reduces macrophage proliferation and accumulation in renal allograft rejection, American Journal of Transplantation, 3, (3) pp. 294-300. ISSN 1600-6135 (2003) [Refereed Article]

Copyright Statement

Copyright 2003 Blackwell Munksgaard

DOI: doi:10.1034/j.1600-6143.2003.00068.x


Macrophage accumulation within an acutely rejecting allograft occurs by recruitment and local proliferation. To determine the importance of M-CSF in driving macrophage proliferation during acute rejection, we blocked the M-CSF receptor, c-fms, in a mouse model of acute renal allograft rejection. C57BL/6 mouse kidneys (allografts, n = 20) or BALB/c kidneys (isografts, n = 5) were transplanted into BALB/c mice. Anti-c-fms antibody (AFS98) or control Ig (50 mg/kg/day, i.p.) was given daily to allografts from days 0-5. All mice were killed day 6 postoperatively. Expression of the M-CSF receptor, c-fms, was restricted to infiltrating CD68+ macrophages. Blockade of c-fms reduced proliferating (CD68+/BrdU+) macrophages by 82% (1.1 v 6.2%, p < 0.001), interstitial CD68+ macrophage accumulation by 53% (595 v 1270/mm2, p < 0.001), and glomerular CD68+ macrophage accumulation by 71% (0.73 V 2.48 CD68+ cells per glomerulus, p < 0.001). Parameters of T-cell involvement (intragraft CD4+, CD8+ and CD25+ lymphocyte numbers) were not affected. The severity of tubulointerstitial rejection was reduced in the treatment group as shown by decreased tubulitis and tubular cell proliferation. Macrophage proliferation during acute allograft rejection is dependent on the interaction of M-CSF with its receptor c-fms. This pathway plays a significant and specific role in the accumulation of macrophages within a rejecting renal allograft.

Item Details

Item Type:Refereed Article
Keywords:allograft rejection
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Nephrology and Urology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Urogenital System and Disorders
UTAS Author:Jose, MD (Professor Matthew Jose)
ID Code:90570
Year Published:2003
Web of Science® Times Cited:48
Deposited By:Medicine
Deposited On:2014-04-10
Last Modified:2014-11-06

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