Opposing effects of in vitro differentiated macrophages sub-type on epithelial wound healing
| Autor: | Samuel Mang, Ingrid Christ, Julia A. Gindele, Juergen Schymeinsky, David J. Lamb, Nicolas Pairet, Florian Gantner |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology Pulmonology Physiology Cellular differentiation Retinoic Acid Retinoic acid lcsh:Medicine Gene Expression Matrix metalloproteinase Biochemistry Epithelium Monocytes Extracellular matrix chemistry.chemical_compound White Blood Cells Fibrosis Cell Movement Animal Cells Medicine and Health Sciences Metabolites lcsh:Science Staining Multidisciplinary biology Cell Staining Cell Differentiation Middle Aged Cell biology Extracellular Matrix Chemistry Phenotype Physical Sciences Airway Remodeling Female Cellular Types Anatomy Research Article medicine.medical_specialty Immune Cells Chronic Obstructive Pulmonary Disease Immunology Motility Bronchi Research and Analysis Methods 03 medical and health sciences ddc:570 Plasminogen Activator Inhibitor 1 Tissue Repair medicine Genetics Humans Cell Proliferation Wound Healing Blood Cells 030102 biochemistry & molecular biology Macrophages lcsh:R Chemical Compounds Biology and Life Sciences Epithelial Cells Cell Biology medicine.disease Coculture Techniques Fibronectin 030104 developmental biology Biological Tissue Metabolism chemistry Specimen Preparation and Treatment Focal Adhesion Protein-Tyrosine Kinases biology.protein lcsh:Q Wound healing Physiological Processes Acids Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 9, p e0184386 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Inappropriate repair responses to pulmonary epithelial injury have been linked to perturbation of epithelial barrier function and airway remodelling in a number of respiratory diseases, including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. We developed an in vitro mechanical scratch injury model in air-liquid interface differentiated primary human small airway epithelial cells that recapitulates many of the characteristics observed during epithelial wound injury in both human tissue and small animal models. Wound closure was initially associated with de-differentiation of the differentiated apical cells and rapid migration into the wound site, followed by proliferation of apical cells behind the wound edge, together with increases in FAK expression, fibronectin and reduction in PAI-1 which collectively facilitate cell motility and extracellular matrix deposition. Macrophages are intimately involved in wound repair so we sought to investigate the role of macrophage sub-types on this process in a novel primary human co-culture model. M1 macrophages promoted FAK expression and both M1 and M2 macrophages promoted epithelial de-differentiation. Interestingly, M2a macrophages inhibited both proliferation and fibronectin expression, possibly via the retinoic acid pathway, whereas M2b and M2c macrophages prevented fibronectin deposition, possibly via MMP expression. Collectively these data highlight the complex nature of epithelial wound closure, the differential impact of macrophage sub-types on this process, and the heterogenic and non-delineated function of these macrophages. published |
| Databáze: | OpenAIRE |
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