Increased generation of TRAP expressing multinucleated giant cells in patients with granulomatosis with polyangiitis

• Published in: PloS one 2012-08, Vol.7 (8), p.e42659-e42659
• Main Authors: Park, Jin Kyun, Askin, Frederic, Giles, Jon T, Halushka, Marc K, Rosen, Antony, Levine, Stuart M
• Format: Article
• Language: English
• Subjects: Acid phosphatase (tartrate-resistant); Acid Phosphatase - genetics; Acid resistance; Adult; Aged; Analysis; Arthritis; Aspartic proteases; Biocompatibility; Biology; Biomedical materials; Biopsy; Biopsy - methods; Blood; Calcitonin; Calcitonin receptors; Case-Control Studies; Cathepsin K; Cathepsins; Cell Separation; Disease control; Enzymes; Female; Flow Cytometry; Gene Expression Regulation, Enzymologic; Genotype & phenotype; Giant cells; Giant Cells - cytology; Giant Cells - metabolism; Granulomatosis; Granulomatosis with Polyangiitis - enzymology; Granulomatosis with Polyangiitis - physiopathology; Humans; Immunohistochemistry; Inflammation; Inflammatory diseases; Isoenzymes - genetics; Leukocytes (mononuclear); Leukocytes, Mononuclear - cytology; Lung - enzymology; Lung - pathology; Lungs; Macrophage colony-stimulating factor; Macrophage Colony-Stimulating Factor - metabolism; Male; Medicine; Middle Aged; Necrosis; Nuclei; Osteoclasts; Osteoclasts - metabolism; Patients; Peripheral blood mononuclear cells; Phenotype; Phenotypes; Phosphatase; Phosphatases; Proteolysis; Proteolytic enzymes; RANK Ligand - metabolism; Receptors; Rheumatology; Subgroups; Tartrate-Resistant Acid Phosphatase; TRANCE protein; Vein & artery diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0042659

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. 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