title: By homing to the kidney, activated macrophages potently exacerbate renal injury.
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 10(6) to 5 x 10(6)) or activated (1 x 10(3) to 1 x 10(6)) 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 10(4) macrophages per mouse compared with control adriamycin nephrotic mice. However, treatment with resting macrophages at doses as high as 5 x 10(6) 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.
authors.affiliation: Centre for Transplantation and Renal Research, The University of Sydney at Westmead Millennium Institute, Westmead, Sydney 2145, Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.forename: Qi
authors.initials: Q
authors.lastname: Cai
authors.forename: Guoping
authors.initials: G
authors.lastname: Zheng
authors.forename: Vincent W S
authors.initials: VW
authors.lastname: Lee
authors.forename: Dong
authors.initials: D
authors.lastname: Zheng
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Li
authors.forename: Thian Kui
authors.initials: TK
authors.lastname: Tan
authors.forename: David C H
authors.initials: DC
authors.lastname: Harris
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004317:Doxorubicin; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000473:pathology; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000637:transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009401:Nephrosis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology
chemical_list: D004317:Doxorubicin