Macrophage accumulation at a site of renal inflammation is dependent on the M-CSF/c-fms pathway.
Production of macrophage-colony stimulating factor (M-CSF), the major macrophage growth factor, is increased in tissues during inflammation. Therefore, we determined whether M-CSF, acting through its receptor c-fms, contributes to macrophage accumulation at a site of tissue injury. Daily treatment with anti-c-fms or control antibody was given to mice with renal inflammation resulting from unilateral ureteric obstruction (UUO). Following UUO, kidney M-CSF mRNA increased in association with macrophage accumulation (days 1, 5, and 10) and local macrophage proliferation (days 5 and 10). Anti-c-fms treatment caused a minor inhibition of monocyte recruitment at day 1, reduced macrophage accumulation by 75% at day 10, but did not affect blood monocyte counts or the CD4 and CD8 lymphocytic infiltrate. Prevention of macrophage accumulation by anti-c-fms treatment was associated with a 90% reduction in local macrophage proliferation at days 5 and 10 without evidence of increased macrophage apoptosis. Therefore, M-CSF/c-fms signaling plays a key role in macrophage accumulation during tissue injury.
Le Meur
Yannick
Y
Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
Tesch
Gregory H
GH
Hill
Prudence A
PA
Mu
Wei
W
Foti
Rita
R
Nikolic-Paterson
David J
DJ
Atkins
Robert C
RC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005786:Gene Expression Regulation; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016131:Lymphocyte Subsets / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000502:physiology*; D015398:Signal Transduction; D014517:Ureteral Obstruction / Q000150:complications
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor