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Granulocyte-CSF links destructive inflammation and comorbidities in obstructive lung disease.
Tsantikos, Evelyn; Lau, Maverick; Castelino, Cassandra Mn; Maxwell, Mhairi J; Passey, Samantha L; Hansen, Michelle J; McGregor, Narelle E; Sims, Natalie A; Steinfort, Daniel P; Irving, Louis B; Anderson, Gary P; Hibbs, Margaret L.
Afiliación
  • Tsantikos E; Department of Immunology and Pathology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
  • Lau M; Department of Immunology and Pathology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
  • Castelino CM; Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Victoria, Australia.
  • Maxwell MJ; Department of Immunology and Pathology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
  • Passey SL; Department of Immunology and Pathology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia.
  • Hansen MJ; Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Victoria, Australia.
  • McGregor NE; Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Victoria, Australia.
  • Sims NA; St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
  • Steinfort DP; St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
  • Irving LB; Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
  • Anderson GP; Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
  • Hibbs ML; Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Victoria, Australia.
J Clin Invest ; 128(6): 2406-2418, 2018 06 01.
Article en En | MEDLINE | ID: mdl-29708507
Chronic obstructive pulmonary disease (COPD) is an incurable inflammatory lung disease that afflicts millions of people worldwide, and it is the fourth leading cause of death. Systemic comorbidities affecting the heart, skeletal muscle, bone, and metabolism are major contributors to morbidity and mortality. Given the surprising finding in large prospective clinical biomarker studies that peripheral white blood cell count is more closely associated with disease than inflammatory biomarkers, we probed the role of blood growth factors. Using the SHIP-1-deficient COPD mouse model, which manifests a syndrome of destructive lung disease and a complex of comorbid pathologies, we have identified a critical and unexpected role for granulocyte-CSF (G-CSF) in linking these conditions. Deletion of G-CSF greatly reduced airway inflammation and lung tissue destruction, and attenuated systemic inflammation, right heart hypertrophy, loss of fat reserves, and bone osteoporosis. In human clinical translational studies, bronchoalveolar lavage fluid of patients with COPD demonstrated elevated G-CSF levels. These studies suggest that G-CSF may play a central and unforeseen pathogenic role in COPD and its complex comorbidities, and identify G-CSF and its regulators as potential therapeutic targets.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor Estimulante de Colonias de Granulocitos / Enfermedad Pulmonar Obstructiva Crónica / Pulmón Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Clin Invest Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor Estimulante de Colonias de Granulocitos / Enfermedad Pulmonar Obstructiva Crónica / Pulmón Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Clin Invest Año: 2018 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos