Phagocytosis of microparticles by alveolar macrophages during acute lung injury requires MerTK
| العنوان: | Phagocytosis of microparticles by alveolar macrophages during acute lung injury requires MerTK |
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| المؤلفون: | Donna L. Bratton, Peter M. Henson, S. Courtney Frasch, William J. Janssen, Alexandria L. McCubbrey, Michael P. Mohning, Stacey M. Thomas, Kara J. Mould, Lea Barthel |
| المصدر: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 314:L69-L82 |
| بيانات النشر: | American Physiological Society, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Physiology, Phagocytosis, Acute Lung Injury, Apoptosis, Inflammation, Biology, Lung injury, Mice, 03 medical and health sciences, Cell-Derived Microparticles, Proto-Oncogene Proteins, Physiology (medical), Macrophages, Alveolar, medicine, Animals, Mice, Knockout, Lung, c-Mer Tyrosine Kinase, Receptor Protein-Tyrosine Kinases, Cell Biology, respiratory system, MERTK, Axl Receptor Tyrosine Kinase, Pathophysiology, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Immunology, Alveolar macrophage, medicine.symptom, Signal Transduction, Research Article |
| الوصف: | Microparticles are a newly recognized class of mediators in the pathophysiology of lung inflammation and injury, but little is known about the factors that regulate their accumulation and clearance. The primary objective of our study was to determine whether alveolar macrophages engulf microparticles and to elucidate the mechanisms by which this occurs. Alveolar microparticles were quantified in bronchoalveolar fluid of mice with lung injury induced by LPS and hydrochloric acid. Microparticle numbers were greatest at the peak of inflammation and declined as inflammation resolved. Isolated, fluorescently labeled particles were placed in culture with macrophages to evaluate ingestion in the presence of endocytosis inhibitors. Ingestion was blocked with cytochalasin D and wortmannin, consistent with a phagocytic process. In separate experiments, mice were treated intratracheally with labeled microparticles, and their uptake was assessed though microscopy and flow cytometry. Resident alveolar macrophages, not recruited macrophages, were the primary cell-ingesting microparticles in the alveolus during lung injury. In vitro, microparticles promoted inflammatory signaling in LPS primed epithelial cells, signifying the importance of microparticle clearance in resolving lung injury. Microparticles were found to have phosphatidylserine exposed on their surfaces. Accordingly, we measured expression of phosphatidylserine receptors on macrophages and found high expression of MerTK and Axl in the resident macrophage population. Endocytosis of microparticles was markedly reduced in MerTK-deficient macrophages in vitro and in vivo. In conclusion, microparticles are released during acute lung injury and peak in number at the height of inflammation. Resident alveolar macrophages efficiently clear these microparticles through MerTK-mediated phagocytosis. |
| تدمد: | 1522-1504 1040-0605 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe72f4e26cf8dce3f2ffaa3cf8771dfd https://doi.org/10.1152/ajplung.00058.2017 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fe72f4e26cf8dce3f2ffaa3cf8771dfd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221504 10400605 |
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