Published online before print May 8, 2008

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Copyright © 2008 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2008.070825

Accepted for publication February 25, 2008.

Article

By Homing to the Kidney, Activated Macrophages Potently Exacerbate Renal Injury

Ying Wang^*, Yiping Wang^*@, Qi Cai^*, Guoping Zheng^*, Vincent W.S. Lee^*, Dong Zheng^*, Xiaomei Li, Thian Kui Tan^*, and David C.H. Harris^*

From the Centre for Transplantation and Renal Research,* The University of Sydney at Westmead Millennium Institute, Westmead, Sydney, Australia; and the Department of Rheumatology and Immunology, Anhui Medical University at Provincial Hospital, Hefei, Anhui, People's Republic of China

^@ To whom correspondence should be addressed. E-mail: Yiping_Wang{at}wsahs.nsw.gov.au.

	Abstract

Macrophages are important mediators of injury in most types of human kidney diseases; however, the pathogenic importance of both macrophage number and activation status is unknown. To examine this question, severe-combined immunodeficient mice with adriamycin nephrosis, an experimental model of human focal segmental glomerulosclerosis, were treated intravenously with either resting (1 x 10⁶ to 5 x 10⁶) or activated (1 x 10³ to 1 x 10⁶) macrophages on day 6 postadriamycin administration, and the effects on kidney injury were examined. On day 28, renal injury was worse in the group that received activated macrophages at doses as low as 1 x 10⁴ macrophages per mouse compared with control adriamycin nephrotic mice. However, treatment with resting macrophages at doses as high as 5 x 10⁶ macrophages per mouse had no significant effect on either renal histology or function. The transferred activated macrophages homed to inflamed kidneys during the middle-to-late stages of the disease, but such homing was not observed for resting macrophages. This study of in vivo cell adoptive transfer supports the importance of macrophage activation status over macrophage number in causing renal injury. These data suggest that therapeutic strategies for treating progressive kidney diseases should target activated macrophages.