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. 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.

[1]  A. Matsumori,et al.  Evidence for a Role of Mast Cells in the Evolution to Congestive Heart Failure , 2002, The Journal of experimental medicine.

[2]  F. Strutz,et al.  Role of mast cell tryptase in renal interstitial fibrosis. , 2001, Journal of the American Society of Nephrology : JASN.

[3]  A. Eddy.  Mast cells find their way to the kidney. , 2001, Kidney international.

[4]  A. E. El Nahas,et al.  Role of stem cell factor and mast cells in the progression of chronic glomerulonephritides. , 2001, Kidney international.

[5]  J. Keski‐Oja,et al.  Activation of paracrine TGF‐β1 signaling upon stimulation and degranulation of rat serosal mast cells: a novel function for chymase , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[6]  B. Rodriguez-Iturbe,et al.  Role of immunocompetent cells in nonimmune renal diseases. , 2001, Kidney international.

[7]  S. Takai,et al.  Mast cell chymase expression and mast cell phenotypes in human rejected kidneys. , 2001, Kidney international.

[8]  M. Cooper,et al.  Diabetes-Induced Vascular Hypertrophy Is Accompanied by Activation of Na+-H+ Exchange and Prevented by Na+-H+ Exchange Inhibition , 2000, Circulation research.

[9]  M. Cooper,et al.  Endothelin receptor antagonism ameliorates mast cell infiltration, vascular hypertrophy, and epidermal growth factor expression in experimental diabetes. , 2000, Circulation research.

[10]  Bruce H. R. Wolffenbuttel,et al.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy , 2000, The Lancet.

[11]  S. Yusuf,et al.  Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[12]  L. Lichtenstein,et al.  RNA Is Closely Associated with Human Mast Cell Secretory Granules, Suggesting a Role(s) for Granules in Synthetic Processes , 2000, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[13]  M. Ihara,et al.  Mast cells in rapidly progressive glomerulonephritis. , 1999, Journal of the American Society of Nephrology : JASN.

[14]  J. Mikovits,et al.  Mast cell migratory response to interleukin-8 is mediated through interaction with chemokine receptor CXCR2/Interleukin-8RB. , 1999, Blood.

[15]  Allen M. Gown,et al.  Complete Chromogen Separation and Analysis in Double Immunohistochemical Stains Using Photoshop-based Image Analysis , 1999, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[16]  H. Shigematsu,et al.  Contribution of mast cells to the tubulointerstitial lesions in IgA nephritis. , 1998, Kidney international.

[17]  M. Kurosawa,et al.  Tubulointerstitial mast cell infiltration in glomerulonephritis. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[18]  David W. Johnson,et al.  Renal expression of transforming growth factor-β inducible gene-h3 (βig-h3) in normal and diabetic rats1 , 1998 .

[19]  J. Rosenbaum,et al.  Ultrastructural Immunolocalization of Basic Fibroblast Growth Factor in Mast Cell Secretory Granules: Morphological Evidence for bFGF Release Through Degranulation , 1998, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[20]  M. Cooper,et al.  A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2)27 rat (TGR). , 1998, Kidney international.

[21]  Möller,et al.  Comparative cytokine gene expression: regulation and release by human mast cells , 1998, Immunology.

[22]  L. Gesualdo,et al.  Progression of renal damage in human glomerulonephritides: is there sleight of hand in winning the game? , 1997, Kidney International.

[23]  David A. Mankoff,et al.  Application of Photoshop-based Image Analysis to Quantification of Hormone Receptor Expression in Breast Cancer , 1997, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[24]  Weber Kt.  Fibrosis, a common pathway to organ failure: angiotensin II and tissue repair. , 1997 .

[25]  M. Cooper,et al.  Transforming growth factor β1 and renal injury following subtotal nephrectomy in the rat: Role of the renin-angiotensin system , 1997 .

[26]  F. Levi-Schaffer,et al.  The human mast cell. , 1997, The Journal of allergy and clinical immunology.

[27]  K. Weber.  Fibrosis, a common pathway to organ failure: angiotensin II and tissue repair. , 1997, Seminars in nephrology.

[28]  S. Galli,et al.  Stem-cell factor, the kit ligand, induces direct degranulation of rat peritoneal mast cells in vitro and in vivo: dependence of the in vitro effect on period of culture and comparisons of stem-cell factor with other mast cell-activating agents. , 1995, Immunology.

[29]  F. Levi-Schaffer,et al.  Mast cell role in fibrotic diseases. , 1995, Israel journal of medical sciences.

[30]  G. Nilsson,et al.  Stem cell factor is a chemotactic factor for human mast cells. , 1994, Journal of immunology.

[31]  B. Gruber.  Mast cells in scleroderma. , 1994, Clinics in dermatology.

[32]  R. Kew,et al.  Transforming growth factor-beta 1 mediates mast cell chemotaxis. , 1994, Journal of immunology.

[33]  P. Valent,et al.  The riddle of the mast cell: kit(CD117)-ligand as the missing link? , 1994, Immunology today.

[34]  R. Atkins,et al.  Macrophages in renal injury. , 1994, Kidney international. Supplement.

[35]  K. Sharma,et al.  The transforming growth factor-beta system and the kidney. , 1993, Seminars in nephrology.

[36]  Brenner Bm.  Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. , 1983 .

[37]  B. Brenner,et al.  Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. , 1983, Kidney international.

[38]  R. Buñag.  Validation in awake rats of a tail-cuff method for measuring systolic pressure. , 1973, Journal of applied physiology.