Figure 3.

Pretreatment with a c-fms inhibitor reduces the number of kidney CD11b⁺/F4/80 cells, inflammation and kidney injury. (A) Schematic representation of preventative treatment with a c-fms inhibitor (c-fms inh) to deplete monocyte/macrophages during the injury phase of disease. Animals were dosed at 30 mg/kg, PO 16 hours and 2 hours prior to surgery and 30 min postreperfusion. (B) Flow-cytometric analysis of total kidney CD11b⁺/F4/80⁺ cells at 24 hours postreperfusion indicates that treatment results in reduced numbers in both injured and normal mice. (C) Reduced circulating levels of monocytes persists at 24 hours. (D) Plasma creatinine indicates that there is reduced loss of kidney function with treatment. Similarly, (E) qRT-PCR of markers of kidney structural injury KIM-1 and NGAL (data not shown) are significantly reduced. (F) qRT-PCR of IL-6 and (G) CXCL1 indicate that the c-fms inhibitor dampens the expression of both cytokines at 2 hours postreperfusion while IL-6 remains reduced through 1 day postreperfusion. *P≤0.05 indicates a significant difference from the respective vehicle group. n=9 for vehicle, I/R, n=10 for c-fms inhibitor, I/R, n=4 for normals.