Abstract: FR-PO1040
BM-Transplant Mouse Model of MPO-ANCA-GPA
Session Information
- Glomerular Diseases: Immunology and Inflammation - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
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