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Increased Generation of TRAP Expressing Multinucleated Giant Cells in Patients with Granulomatosis with Polyangiitis
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 l...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414441/ https://www.ncbi.nlm.nih.gov/pubmed/22905158 http://dx.doi.org/10.1371/journal.pone.0042659 |
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author | Park, Jin Kyun Askin, Frederic Giles, Jon T. Halushka, Marc K. Rosen, Antony Levine, Stuart M. |
author_facet | Park, Jin Kyun Askin, Frederic Giles, Jon T. Halushka, Marc K. Rosen, Antony Levine, Stuart M. |
author_sort | Park, Jin Kyun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3414441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34144412012-08-19 Increased Generation of TRAP Expressing Multinucleated Giant Cells in Patients with Granulomatosis with Polyangiitis Park, Jin Kyun Askin, Frederic Giles, Jon T. Halushka, Marc K. Rosen, Antony Levine, Stuart M. PLoS One Research Article 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. Public Library of Science 2012-08-08 /pmc/articles/PMC3414441/ /pubmed/22905158 http://dx.doi.org/10.1371/journal.pone.0042659 Text en © 2012 Park et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Park, Jin Kyun Askin, Frederic Giles, Jon T. Halushka, Marc K. Rosen, Antony Levine, Stuart M. Increased Generation of TRAP Expressing Multinucleated Giant Cells in Patients with Granulomatosis with Polyangiitis |
title | Increased Generation of TRAP Expressing Multinucleated Giant Cells in Patients with Granulomatosis with Polyangiitis |
title_full | Increased Generation of TRAP Expressing Multinucleated Giant Cells in Patients with Granulomatosis with Polyangiitis |
title_fullStr | Increased Generation of TRAP Expressing Multinucleated Giant Cells in Patients with Granulomatosis with Polyangiitis |
title_full_unstemmed | Increased Generation of TRAP Expressing Multinucleated Giant Cells in Patients with Granulomatosis with Polyangiitis |
title_short | Increased Generation of TRAP Expressing Multinucleated Giant Cells in Patients with Granulomatosis with Polyangiitis |
title_sort | increased generation of trap expressing multinucleated giant cells in patients with granulomatosis with polyangiitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414441/ https://www.ncbi.nlm.nih.gov/pubmed/22905158 http://dx.doi.org/10.1371/journal.pone.0042659 |
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