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Kidney Week

Abstract: TH-PO086

Neutrophil Depletion Alters Macrophage (Mo) Phenotype and Modulates Inflammation in Unilateral Ureteral Obstructed (UUO) Kidney

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Ghosh, Siddhartha S., VCU Medical Ctr, Richmond, Virginia, United States
  • Gonzalez, Austin J., Virginia Commonwealth University, Fredericksburg, Virginia, United States
  • Krieg, Richard, VCU, Richmond, Virginia, United States
  • Gehr, Todd W., Virginia Commonwealth University, Fredericksburg, Virginia, United States

UUO is a model to study inflammation and fibrosis in the kidney. Neutrophils (Neu) are the first line of defense in response to injury. Mo closely coordinate with Neu to regulate inflammation. This study investigated if neutrophil depletion can alter macrophage infiltration and inflammation in UUO fibrosis.


UUO surgery was done by the method adapted from the Vanderbilt O’Brien Center. Neutrophil depletion was done by injecting clone 1A8 to a cohort of five mice labeled (ND), 3 days pre and 2 days post UUO. An equal number of mice underwent UUO but did not receive any treatment (UT). Contralateral kidneys were used as control (C). Mice were sacrificed 3 days and 10 days after UUO. Neu, Mo, and macrophage phenotype M1 and M2 were determined by flow cytometry. Inflammation markers MCP1, IL1β, and fibrosis marker α-smooth muscle actin (SMA) were assessed by immunoblot.


There was no significant influx of Mo and trace levels of inflammatory markers in C, hence comparison was made between ND and UT. 3 days after UUO, Neu levels in the blood and kidney of UT were 28% and 60% respectively. In contrast, Neu levels in ND blood and kidney was <1% and <12% respectively, suggesting significant neutrophil depletion. 3 Day UUO: Mo influx in the kidney of ND was significantly lower than UT. The M1 phenotype in UT was 1.5 fold higher (p<0.05) and M2 phenotype was 2 fold lower than ND (p<0.05). Kidney MCP-1 and IL-1β of UT was 3 fold (p<0.01) and 2.5 fold (p<0.01) higher than ND, respectively. Kidney SMA was not significantly altered between the groups. 10-day UUO: The M1 phenotype in UT was still 1.5 fold higher (p<0.05) than ND but the difference in M2 phenotype between UT and ND was not significant. MCP-1 and IL-1β were 2 and 1.5 (p<0.05) fold higher in UT, suggesting sustained inflammation in UT. SMA levels in the ND kidney were 1.8 fold higher than UT but was not statistically significant.


Chronic inflammation frequently leads to fibrosis, however, the mechanisms are not clearly understood. In the ND cohort the decrease in M1 phenotype (thought to be proinflammatory) and increase in M2 (reparative type) following neutrophil depletion can explain the reduced inflammation but not fibrosis. This suggests controlling inflammation at an early stage may not positively modulate fibrosis.