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. CONCLUSION: Mast cell infiltration and related chemokine expression are prominent and early features following renal mass reduction and may contribute pathogenetically to progressive renal injury.
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. CONCLUSION: Mast cell infiltration and related chemokine expression are prominent and early features following renal mass reduction and may contribute pathogenetically to progressive renal injury.
Authors: José A Roldão; Marcela Beghini; Luciana S Ramalho; Carla Souza Porto; Denise B R Rodrigues; Vicente P A Teixeira; Sanívia A de Lima Pereira Journal: Parasitol Res Date: 2012-03-13 Impact factor: 2.289
Authors: Arul Veerappan; Alicia C Reid; Nathan O'Connor; Rosalia Mora; Jacqueline A Brazin; Racha Estephan; Takashi Kameue; Jie Chen; Diane Felsen; Surya V Seshan; Dix P Poppas; Thomas Maack; Randi B Silver Journal: Am J Physiol Renal Physiol Date: 2011-09-28