Figure 4
Figure 4. Sickle chimeras with low FII levels are protected against kidney damage and sickle nephropathy. (A-F) Representative H&E kidney sections comparisons between HbS/FIIWT (left panel) and HbS/FIIlox/− (right panel) mice showing (A) ischemia, inflammatory cell infiltration, and renal scarring (×10 objective). (B-C) FSGS and glomerular atrophy (shown by arrows) in HbS/FIIWT glomeruli compared with HbS/FIIlox/− glomeruli. (D-E) PAS staining showing glomerular basement membrane thickening in HbS/FIIWT glomeruli compared with HbS/FIIlox/− glomeruli. (F) Representative H&E-stained sections of renal tubules showing tubular loss, inflammatory cell infiltration (indicated by dotted lines), and regenerative tubules. (B-F) Objective, ×60. (G-J) Semiquantitative assessment of histologic features. Histology scores ranged from 0 to 5, where 0 represented normal kidney morphology; 1, changes in <15% of glomerular area; 2, 20% to 30% of the glomerular area; 3, 40% to 50% of the glomerular area; 4, ∼60% to 70% of glomerular area; 5, severe changes in most all glomeruli. (K) Urine albumin and (L) urine osmolality values. Mice used as transplant recipients were of similar ages (8-10 weeks) with equal numbers of males and females distributed among the experimental groups. Fully chimeric sickle or normal mice were followed for a year posttransplantation. Each symbol represents an individual animal. Statistical analyses on the histologic scores were done by Mann-Whitney U test. Statistical significance between HbS/FIIWT (n = 6) and HbS/FIIlox/− (n = 7) mice is indicated by asterisks: ****P < .0001, ***P < .01, **P < .01, *P < .05.

Sickle chimeras with low FII levels are protected against kidney damage and sickle nephropathy. (A-F) Representative H&E kidney sections comparisons between HbS/FIIWT (left panel) and HbS/FIIlox/− (right panel) mice showing (A) ischemia, inflammatory cell infiltration, and renal scarring (×10 objective). (B-C) FSGS and glomerular atrophy (shown by arrows) in HbS/FIIWT glomeruli compared with HbS/FIIlox/− glomeruli. (D-E) PAS staining showing glomerular basement membrane thickening in HbS/FIIWT glomeruli compared with HbS/FIIlox/− glomeruli. (F) Representative H&E-stained sections of renal tubules showing tubular loss, inflammatory cell infiltration (indicated by dotted lines), and regenerative tubules. (B-F) Objective, ×60. (G-J) Semiquantitative assessment of histologic features. Histology scores ranged from 0 to 5, where 0 represented normal kidney morphology; 1, changes in <15% of glomerular area; 2, 20% to 30% of the glomerular area; 3, 40% to 50% of the glomerular area; 4, ∼60% to 70% of glomerular area; 5, severe changes in most all glomeruli. (K) Urine albumin and (L) urine osmolality values. Mice used as transplant recipients were of similar ages (8-10 weeks) with equal numbers of males and females distributed among the experimental groups. Fully chimeric sickle or normal mice were followed for a year posttransplantation. Each symbol represents an individual animal. Statistical analyses on the histologic scores were done by Mann-Whitney U test. Statistical significance between HbS/FIIWT (n = 6) and HbS/FIIlox/− (n = 7) mice is indicated by asterisks: ****P < .0001, ***P < .01, **P < .01, *P < .05.

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