Kidney Week

Abstract: TH-PO265

A Distinct Kidney CD45intCD11bintF4/80+MHCII+Ly6C- Macrophage Population in Mice and Humans

Session Information

• AKI Basic: Inflammation and Transcription
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Acute Kidney Injury

• 001 AKI: Basic

Authors

• Lee, Sul A, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Sul A Lee,

• Noel, Sanjeev, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Sanjeev Noel,

• Sadasivam, Mohanraj, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Mohanraj Sadasivam,

• Hamad, Abdel, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Abdel Hamad,

• Rabb, Hamid, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Hamid Rabb,

Background

Kidney mononuclear phagocytic cells (MPCs) play important roles in the pathogenesis of acute kidney injury (AKI) and other inflammatory diseases. However, renal MPCs are incompletely understood. While focusing on murine kidney TCRαβ⁺CD4^-CD8^- [double negative (DN)] T cells, we identified a distinct kidney macrophage subset which differed from conventional renal macrophages in many key aspects.

Methods

MPCs were isolated from different lymphoid and non-lymphoid organs of C57BL6 male mice at baseline or following ischemic AKI and analyzed for the frequency and phenotypic markers. Macrophage ablation was performed by intraperitoneal injection of liposomal clodronate. MPCs in human kidney were analyzed in normal tissue from nephrectomies for renal cell carcinoma.

Results

While focusing on kidney DN T cells, we identified a cell population that binds only to TCRβ and CD8β antibodies but not to CD8α antibody. Further studies using Fc receptor blockers disclosed that this population was a renal macrophage subset which was different from conventional macrophages by its intermediate (int) expression of CD45 and CD11b. These CD45^intCD11b^int macrophages were further characterized as F4/80⁺MHCII⁺Ly6C^- cells, comprising 16.8%±0.4% of total CD45⁺ cells in normal kidney (P = 0.002), 4.5%±1.0% in heart but <1% of total CD45⁺ cells in thymus, lymph node, spleen, lung, liver, lamina propria and intraepithelial layer. Systemic clodronate treatment had greater depletive effect on CD45^intCD11b^int population than conventional CD45^highCD11b⁺ population (77.1% vs. 19.3%) in mouse kidney, suggesting higher phagocytic function of CD45^intCD11b^int population. CD45^intCD11b^int cells increased rapidly after AKI and decreased after 48 hours compared to a persistent increase in CD45^highCD11b⁺ population (P < 0.05). We also found CD45^intCD11b^int macrophages (1.4% to 9.3%) in human kidney samples (n=3) compared to conventional CD45^highCD11b⁺ population that comprised 12.5% to 42.4% of total CD45⁺ cells.

Conclusion

Our data suggest that CD45^intCD11b^intF4/80⁺MHCII⁺Ly6C^- macrophages are primarily found in kidney and have distinct pattern of phenotypic markers and response to ischemic AKI compared to traditional macrophages. We are currently studying functional characteristics of this population by analyzing their phagocytosis functions, cytokines, and role in kidney diseases.

Funding

• NIDDK Support