Platelets are not critical effector cells for the time course of murine passive crescentic glomerulonephritis. (June 2013)

• Record Type: Journal Article
• Authors: Hohenstein, Bernd; Daniel, Christoph; Johnson, Richard J.; Amann, Kerstin U.; Hugo, Christian P. M.
• Is Part Of: Platelets. Volume 24:Number 4(2013:Jun.)
• Page Start: 267
• Page End: 274
• Publication Date: 2013-06
• Subjects: Blood platelets -- Periodicals; Blood Platelets -- Periodicals; 615.39
• DOI: 10.3109/09537104.2012.684731
• Languages: English
• ISSNs: 0953-7104

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>vs.</italic> 42/nl; <italic>P</italic> < 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.</p> </abstract>