Figure 4.

Spleen tyrosine kinase (SYK) inhibition improves renal histopathology in experimental autoimmune vasculitis (EAV). (a) Quantification of glomerular abnormalities at treatment initiation (week 4 [W4]) and at 6 weeks after disease induction, with (c) representative photomicrographs demonstrating focal necrotizing glomerulonephritis and crescent formation in vehicle-treated animals and preserved glomerular histology after fostamatinib (Fosta) treatment (periodic acid–Schiff [PAS]–stained sections, original magnification ×400). (b) Quantification of ED-1 (rat homologue of CD68)–positive cells infiltrating glomeruli at treatment initiation (W4) and at 6 weeks after disease induction, showing a dose-dependent reduction with fostamatinib treatment, with representative photomicrographs demonstrating immunoperoxidase staining for ED-1 (b; with hematoxylin counterstain; original magnification ×400). (d) Heat-map indicating changes in intra-renal gene expression following treatment with fostamatinib, as determined by real-time quantitative polymerase chain reaction and expressed as fold-change compared to normal kidney tissue. All data are reported as median ± interquartile range; statistical comparison by Mann-Whitney or Kruskal-Wallis test, with Dunn’s post-test comparison to vehicle group (lower indicator); ∗P < 0.05; ∗∗P < 0.01; ∗∗∗P < 0.0001. CCL3, C–C motif chemokine ligand 3; CFA, complete Freunds adjuvant; MCP-1, monocyte chemoattractant protein 1; MMP9, matrix metallopeptidase 9; ns, not significant; TNF, tumor necrosis factor. To optimize viewing of this image, please see the online version of this article at www.kidney-international.org.