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Pulmonary osteoclast-like cells in silica induced pulmonary fibrosis.
Hasegawa, Yoshihiro; Franks, Jennifer M; Tanaka, Yusuke; Uehara, Yasuaki; Read, David F; Williams, Claire; Srivatsan, Sanjay; Pitstick, Lori B; Nikolaidis, Nikolaos M; Shaver, Ciara M; Kropski, Jonathan; Ware, Lorraine B; Taylor, Chase J; Banovich, Nicholas E; Wu, Huixing; Gardner, Jason C; Osterburg, Andrew R; Yu, Jane J; Kopras, Elizabeth J; Teitelbaum, Steven L; Wikenheiser-Brokamp, Kathryn A; Trapnell, Cole; McCormack, Francis X.
Afiliação
  • Hasegawa Y; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Franks JM; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Tanaka Y; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Uehara Y; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Read DF; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Williams C; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Srivatsan S; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
  • Pitstick LB; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Nikolaidis NM; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Shaver CM; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Kropski J; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Ware LB; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Taylor CJ; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Banovich NE; Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Wu H; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Gardner JC; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Osterburg AR; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Yu JJ; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Kopras EJ; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • Teitelbaum SL; Department of Pathology and Immunology, and Division of Bone and Mineral Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Wikenheiser-Brokamp KA; Division of Pathology and Laboratory Medicine and Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Trapnell C; Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA.
  • McCormack FX; Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Sci Adv ; 10(28): eadl4913, 2024 Jul 12.
Article em En | MEDLINE | ID: mdl-38985878
ABSTRACT
The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of bone-resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoclastos / Fibrose Pulmonar / Silicose / Diferenciação Celular / Dióxido de Silício Limite: Animals / Female / Humans / Male Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoclastos / Fibrose Pulmonar / Silicose / Diferenciação Celular / Dióxido de Silício Limite: Animals / Female / Humans / Male Idioma: En Revista: Sci Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos