ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: FR-PO1040

BM-Transplant Mouse Model of MPO-ANCA-GPA

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Alba, Marco A., UNC-Chapel Hill, Chapel Hill, North Carolina, United States
  • Hu, Peiqi, UNC-Chapel Hill, Chapel Hill, North Carolina, United States
  • Xiao, Hong, UNC-Chapel Hill, Chapel Hill, North Carolina, United States
  • Falk, Ronald J., UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Jennette, J. Charles, UNC-Chapel Hill, Chapel Hill, North Carolina, United States
Background

Granulomatosis with polyangiitis is an ANCA-vasculitis characterized by necrotizing granulomatous inflammation and small vessel vasculitis. Pathogenic mechanisms involved in the development of GPA remain poorly understood. Therefore, we sought to develop a reliable murine GPA model.

Methods

MPO-knockout mice (n=8) previously immunized with mouse MPO were exposed to lethal irradiation, followed by transplantation of MPO-expressing bone marrow (1.5x107 BM cells); resulting in circulating anti-MPO antibodies and MPO+ neutrophils. Lipopolysaccharide (LPS, 5µg) was administered by intratracheal instillation 3 weeks after BM transplant; mice were euthanized one week after.

Results

Engraftment of MPO-positive BM in combination of IT LPS resulted in the development of typical pulmonary and kidney ANCA-associated lesions in various phases of evolution, i.e., lung granulomatous lesions and vasculitis in addition to necrotizing crescentic glomerulonephritis (Figure 1).

Conclusion

A reproducible mouse model of MPO-ANCA-GPA is reported. Our results demonstrate that: 1) LPS functions as synergistic pro-inflammatory factor for facilitating anti-MPO induced pulmonary granulomatosis and 2) The effect of long-term exposure to anti-MPO-ANCA resulted in lung and kidney inflammatory lesions of different ages of evolution, closely mimicking human disease.

Funding

  • Other NIH Support