Mast cell infiltration and chemokine expression in progressive renal disease.
BACKGROUND
Mast cells are growth factor-rich, bone marrow-derived cells that infiltrate injured tissue where they have been implicated in the pathogenesis of progressive fibrosis.


METHODS
Mast cell infiltration and the expression of related chemoattractants was examined following 5/6 nephrectomy, a model of progressive, nonimmune-mediated renal injury. In addition, expression of the profibrotic cytokine, transforming growth factor-beta (TGF-beta) within mast cells and the effects of renoprotective therapy with angiotensin-converting enzyme (ACE) inhibition were also determined.


RESULTS
Renal injury was accompanied by mast cell infiltration, in close proximity to areas of tubulointerstitial fibrosis. Mast cells displayed toluidine blue metachromasia and were immunopositive for TGF-beta1 as well as chymase and tryptase. The expression of several mast cell chemokines, including stem cell factor, interleukin-8 (IL-8), and also TGF-beta1, were increased in 5/6 nephrectomized kidneys. ACE inhibition with ramipril led to a reduction in renal injury in association with attenuation of mast cell infiltration and chemokine expression.


CONCLUSIONS
Mast cell infiltration and related chemokine expression are prominent and early features following renal mass reduction and may contribute pathogenetically to progressive renal injury.
Jones
Susan E
SE
University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia.
Kelly
Darren J
DJ
Cox
Alison J
AJ
Zhang
Yuan
Y
Gow
Renae M
RM
Gilbert
Richard E
RE
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D018450:Disease Progression; D016209:Interleukin-8 / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology*; D009392:Nephrectomy / Q000379:methods; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019089:Stem Cell Factor / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D000806:Angiotensin-Converting Enzyme Inhibitors; D018925:Chemokines; D016209:Interleukin-8; D019089:Stem Cell Factor; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017257:Ramipril