Abstract: TH-PO1074

SLC26A6 Is the Principal Oxalate Transporter in Macrophages

Session Information

Category: Mineral Disease

  • 1204 Mineral Disease: Nephrolithiasis

Authors

  • Wagner, Teresa Raphaela, Yale School of Medicine, New Haven, United States
  • Tonner, Louise Maida, FAU Erlangen, Erlangen, Germany
  • Jiang, Zhirong, Yale School of Medicine, New Haven, Connecticut, United States
  • Thomson, Robert Brent, Yale School of Medicine, New Haven, Connecticut, United States
  • Knauf, Felix, University Hospital Charite, Berlin, Germany
  • Aronson, Peter S., Yale School of Medicine, New Haven, Connecticut, United States
Background

Macrophages are able to phagocytose calcium oxalate crystals, dissolve the crystals into their molecular components, and discharge accumulated oxalate. The goal of this study was to identify the transporter(s) responsible for oxalate transport across the plasma membrane of macrophages. We specifically evaluated the potential role of SLC26A6 because of its known activity as a Cl--oxalate exchanger in kidney and intestine.

Methods

Oxalate transport in macrophages was assessed by using the human monocytic THP-1 cell line and bone marrow-derived macrophages from mice in 14C-oxalate transport assays. Immunoblotting and qPCR were used to detect expression of SLC26A6. The functional role of SLC26A6 in mediating oxalate transport was studied by siRNA knockdown in THP-1 cells and isolation of macrophages from Slc26a6-/- mice. Macrophage viability was measured by WST-1 assays.

Results

DIDS-sensitive Cl- gradient-stimulated oxalate transport was detected in both THP-1 cells and mouse macrophages, consistent with Cl--oxalate exchange activity. Expression of SLC26A6 in THP-1 cells and mouse macrophages was detected by qPCR and immunoblotting. Partial knockdown of SLC26A6 expression by siRNA in THP-1 cells caused significant reduction of Cl--oxalate exchange activity. There was complete loss of Cl--oxalate exchange activity in macrophages isolated from Slc26a6-/- mice. Prolonged incubation with 14C-oxalate revealed significantly higher accumulation of oxalate in macrophages from Slc26a6-/- mice compared to wild-type mice, indicating that SLC26A6 plays a major role in mediating oxalate efflux under physiological conditions. Moreover, incubation in high oxalate media was found to cause significantly greater loss of viability of macrophages from Slc26a6-/- mice compared to wild-type mice.

Conclusion

We conclude that SLC26A6 is the principal oxalate transporter in macrophages and likely plays a role in mediating oxalate efflux and reducing cellular oxalate toxicity.

Funding

  • NIDDK Support