Related Experiment Video
Updated: May 19, 2026
An Immunohistopathologic Study to Profile the Folate Receptor Beta Macrophage and Vascular Immune Microenvironment in Giant Cell Arteritis
Published on: February 8, 2019
Increased generation of TRAP expressing multinucleated giant cells in patients with granulomatosis with polyangiitis
Jin Kyun Park1, Frederic Askin, Jon T Giles
1Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. jinkyunpark@gmail.com
Background:
Tissue-infiltrating multinucleated giant cells (MNGs) within geographic necrosis are pathologic hallmarks of granulomatosis with polyangiitis (GPA). However, the origin, phenotype, and function of these cells in GPA remain undefined.
Methodology/Principal Findings:
MNG phenotype in GPA lung tissue was examined by immunohistochemistry using antibody directed against cathepsin K and calcitonin-receptor. Tartrate-resistant-acid-phosphatase (TRAP) expression was assessed using enzymatic color reaction. Peripheral blood mononuclear cells (PBMCs) from 13 GPA patients (5 with localized and 8 with systemic disease) and 11 healthy controls were cultured in the presence of RANKL and M-CSF for 9 days, and TRAP+ MNGs containing 3 or more nuclei were identified. GPA lung granulomata contained numerous MNGs that expressed osteoclastic TRAP and cathepsin K but not calcitonin receptors. In the presence of RANKL and M-CSF, PBMCs of GPA patients formed significantly more MNGs than healthy controls (114 ± 29 MNG/well vs. 22 ± 9 MNG/well, P = 0.02). In a subgroup analysis, patients with systemic disease generated significantly more MNGs than patients with localized disease (161 ± 35 MNG/well vs. 39 ± 27 MNG/well, P<0.01) or healthy controls (P<0.01). MNG production did not differ between localized GPA and control subjects (P = 0.96).
Conclusions/Significance:
MNGs in granulomata in the GPA lung express osteoclastic enzymes TRAP and cathepsin K. GPA patients have a higher propensity to form TRAP+ MNGs from peripheral blood than healthy controls. These data suggest that (i) the tendency to form MNGs is a component of the GPA phenotype itself, and (ii) that lesional MNGs might participate in the destructive process through their proteolytic enzymes.
Insights
Multinucleated giant cells (MNGs) in granulomatosis with polyangiitis (GPA) express osteoclastic enzymes. GPA patients show increased MNG formation, suggesting a role in disease pathology.
Area of Science:
- Immunology
- Pathology
- Rheumatology
Background:
- Multinucleated giant cells (MNGs) in granulomatosis with polyangiitis (GPA) lung tissue are characteristic but their origin and function are unknown.
- Understanding MNGs is crucial for deciphering GPA pathogenesis.
Purpose of the Study:
- To investigate the phenotype and origin of MNGs in GPA lung tissue.
- To compare MNG formation capacity between GPA patients and healthy individuals.
Main Methods:
- Immunohistochemistry was used to analyze MNG phenotype in GPA lung tissue.
- Peripheral blood mononuclear cells (PBMCs) from GPA patients and controls were cultured with RANKL and M-CSF to assess MNG formation.
- Tartrate-resistant-acid-phosphatase (TRAP), cathepsin K, and calcitonin receptor expression were evaluated.
Main Results:
- GPA lung granulomata contained MNGs expressing osteoclastic TRAP and cathepsin K, but not calcitonin receptors.
- PBMCs from GPA patients formed significantly more TRAP+ MNGs compared to healthy controls.
- Patients with systemic GPA generated more MNGs than those with localized GPA or controls.
Conclusions:
- MNGs in GPA lungs exhibit an osteoclast-like phenotype with expression of TRAP and cathepsin K.
- GPA patients demonstrate an increased propensity for MNG formation, indicating it's part of the GPA phenotype.
- Lesional MNGs may contribute to tissue destruction via their proteolytic enzymes.
