Platelets are not critical effector cells for the time course of murine passive crescentic glomerulonephritis.
Although platelets are well-known effector cells of inflammatory renal disease, clinical studies were not able to establish platelet inhibition as an effective therapy. Our previous studies using Vasodilator stimulated Phosphoprotein- and P2Y1-deficient mice suggested some early, but no long-term effects of platelets in passive crescentic glomerulonephritis. To define the role of platelets for this disease model, passive crescentic glomerulonephritis was induced in 72 C57Bl/6 mice by intraperitoneal injection of sheep anti-rabbit glomerular basement membrane antibody on 2 consecutive days. Platelets were depleted using anti-glycoprotein Ibα antibodies (p0p3/p0p4) every 4th day. Mice treated with equal amounts of sterile Phosphate buffered solution or rat-IgG served as controls. Blood, urine, and tissues were harvested on days 3 and 28. Renal tissue sections were evaluated after immunostaining using (semi)quantitative and computer-assisted image analysis. Compared to controls, efficient depletion was achieved as indicated by a markedly prolonged bleeding time and a more than 90% reduction in platelet counts (800/nl vs. 42/nl; P < 0.001). Functional (creatinine-clearance and proteinuria) parameters demonstrated no significant differences between the groups. Neither parameters of renal injury (glomerulosclerosis and fibrosis) nor glomerular/tubulointerstitial matrix expansion (by collagen IV staining), glomerular capillary rarefaction (lectin staining), and the glomerular/tubulointerstitial proliferative response (proliferating cell nuclear antigen) demonstrated any differences between platelet-depleted mice and PBS- or rat-IgG-treated nephritic mice at any time point. Despite effective platelet inhibition/depletion, neither the short- nor long-term course of passive crescentic nephrotoxic nephritis was affected. These data indicate that platelets play a minor role during the time course of this disease model in the mouse.
Division of Nephrology, Department of Internal Medicine III, University of Technology, Dresden, Germany. bernd.hohenstein@uniklinikumdresden.de
Bernd
B
Hohenstein
Christoph
C
Daniel
Richard J
RJ
Johnson
Kerstin U
KU
Amann
Christian P M
CP
Hugo
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology*; D002196:Capillaries / Q000276:immunology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D019038:Platelet Glycoprotein GPIb-IX Complex
D001323:Autoantibodies; D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor