Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span
نویسندگان
چکیده
Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion.
منابع مشابه
THE ROLE OF ALVEOLAR MACROPHAGES IN THE PRODUCTION OF COLONY –STIMULATING FACTOR BY THE LUNG
The role of alveolar macrophages in the production of granulocyte/ macrophage colony-stimulating factor(s) by the rat lung was investigated. Lavaged lungs, when incubated at proper weight per volume of culture medium, produced the same amount of colony-stimulating factor as unlavaged ones. Both lavaged and unlavaged lungs produced similar types of colony-stimulating factor (s). Prolonged i...
متن کاملEffect of thalidomide on the alveolar epithelial cells in the lung fibrosis induced by bleomycin in mice
Introduction: Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and usually fatal lung disease of unknown etiology for which no effective treatments currently exist. In the adults type I and II pneumocytes, forms Components of the alveolar epithelial cells. In this study, we investigated the effect of thalidomide on the alveolar epithelial cells (type I and II pneumocytes) in ...
متن کاملبررسی تغییرات گلیکو پروتئین های سطح سلولی ماکروفاژهای ریه در بیماری های فیبروز ریوی
Introduction: The respiratory system is both a route of entry and exit for toxins and injurious agents, as well as being a target for chemical substances and pathogens. Therefore, an understanding of the structure and function of the migratory cell populations of pulmonary tissues including alveolar macrophages is central in a number of important disease processes. This study aimed to identify ...
متن کاملQuantification and comparison of TLR2 activity in monocyte-derived macrophages of zebu and crossbred cattle
The present study was conducted to quantify and compare TLR2 (toll-like receptor 2) activity in monocyte-derived macrophages of zebu (Tharparkar) and crossbred (Holstein-Friesian × Jersey × Brown Swiss × Hariana) cattle. The cells were either induced with Pam3CSK4 or kept as control. The TLR2 activity was quantified in terms of IκB-α inhibitory subunit (NFKBIA) messenger RNA (mRNA) copies...
متن کاملProcoagulant (thromboplastin) activity in human bronchoalveolar lavage fluids is derived from alveolar macrophages.
Fibrin deposition in the alveolar space and the lung interstitium is a prominent feature of many types of inflammatory pulmonary diseases. Cells of the monocyte/macrophage line are the primary cells supplying procoagulant activity in inflammatory lesions. In the present study we found that both lung alveolar macrophages (LAM) and bronchoalveolar lavage fluids (BALF) from humans contained procoa...
متن کامل