RESUMO
The numbers of macrophages are increased in the lungs of chronic obstructive pulmonary disease (COPD) patients. COPD lung macrophages have reduced ability to phagocytose microbes and efferocytose apoptotic cells. Inhaled corticosteroids (ICSs) are widely used anti-inflammatory drugs in COPD; however, their role beyond suppression of cytokine release has not been explored in COPD macrophages. We have examined the effects of corticosteroids on COPD lung macrophage phenotype and function. Lung macrophages from controls and COPD patients were treated with corticosteroids; effects on gene and protein expression of CD163, CD164, CD206, MERTK, CD64, CD80 and CD86 were studied. We also examined the effect of corticosteroids on the function of CD163, MERTK and cluster of differentiation 64 (CD64). Corticosteroid increased CD163, CD164, CD206 and MERTK expression and reduced CD64, CD80 and CD86 expression. We also observed an increase in the uptake of the haemoglobin-haptoglobin complex (CD163) from 59 up to 81% and an increase in efferocytosis of apoptotic neutrophils (MERTK) from 15 up to 28% following corticosteroid treatment. We observed no effect on bacterial phagocytosis. Corticosteroids alter the phenotype and function of COPD lung macrophages. Our findings suggest mechanisms by which corticosteroids exert therapeutic benefit in COPD, reducing iron available for bacterial growth and enhancing efferocytosis.
Assuntos
Corticosteroides/farmacologia , Dexametasona/farmacologia , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Células Cultivadas , Técnicas de Cocultura , Feminino , Regulação da Expressão Gênica , Humanos , Ferro/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/patologia , Fenótipo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores de IgG/genética , Receptores de IgG/metabolismo , Transdução de Sinais , c-Mer Tirosina Quinase/genética , c-Mer Tirosina Quinase/metabolismoRESUMO
Occupational lung/thoracic diseases are a major global public health issue. They comprise a diverse spectrum of health conditions with complex pathology, most of which arise following chronic heavy workplace exposures to various mineral dusts, metal fumes, or following inhaled organic particulate reactions. Many occupational lung diseases could become irreversible; thus accurate diagnosis is mandatory to minimize dust exposure and consequently reduce damage to the respiratory system. Lung biopsy is usually required when exposure history is inconsistent with imaging, in case of unusual or new exposures, in case of unexpected malignancy, and in cases in which there are claims for personal injury and legal compensation. In this paper, we provide an overview of the most frequent occupational lung diseases with a focus on pathological diagnosis. This is a paper that summarizes the expert opinion from a group of European pathologists, together with contributions from other specialists who are crucial for the diagnosis and management of these diseases. Indeed, tight collaboration of all specialists involved in the workup is mandatory as many occupational lung diseases are misdiagnosed or go unrecognized. This document provides a guide for pathologists in practice to facilitate the accurate diagnosis of occupational lung disease. The review article reports relevant topics discussed during an educational course held by expert pathologists, active members of the Pulmonary Pathology Working Group of the European Society of Pathology. The course was endorsed by the University of Padova as a "winter school" (selected project in the call for "Shaping a World-class University" 2022).
Assuntos
Pneumopatias , Doenças Profissionais , Patologistas , Humanos , Pneumopatias/diagnóstico , Pneumopatias/patologia , Doenças Profissionais/diagnóstico , Doenças Profissionais/patologia , Exposição Ocupacional/efeitos adversos , Europa (Continente) , Prova PericialRESUMO
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