The metalloproteinase ADAM8 promotes leukocyte recruitment in vitro and in acute lung inflammation
| Autor: | Aaron Babendreyer, Andreas Ludwig, Julian Schumacher, Franz M. Hess, Sandra Fellendorf, Anke Seifert, Joerg W. Bartsch, Jessica Pruessmeyer, Daniela Dreymueller |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Chemokine Pathology medicine.medical_specialty Cell Membrane Permeability Physiology Inflammation 03 medical and health sciences 0302 clinical medicine Antigens CD Physiology (medical) Cell Adhesion Leukocytes Disintegrin medicine Animals Edema Humans RNA Messenger Wound Healing Metalloproteinase Lung biology Chemotaxis Endothelial Cells Membrane Proteins Pneumonia Cell Biology Adhesion In vitro Mice Inbred C57BL ADAM Proteins HEK293 Cells 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Acute Disease biology.protein Cytokines medicine.symptom ADAM8 |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 313:L602-L614 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.00444.2016 |
| Popis: | Alveolar leukocyte recruitment is a hallmark of acute lung inflammation and involves transmigration of leukocytes through endothelial and epithelial layers. The disintegrin and metalloproteinase (ADAM) 8 is expressed on human isolated leukocytic cells and can be further upregulated on cultured endothelial and epithelial cells by proinflammatory cytokines. By shRNA-mediated knockdown we show that leukocytic ADAM8 is required on monocytic THP-1 cells for chemokine-induced chemotaxis as well as transendothelial and transepithelial migration. Furthermore, ADAM8 promotes αL-integrin upregulation and THP-1 cell adhesion to endothelial cells. On endothelial cells ADAM8 enhances transendothelial migration and increases cytokine-induced permeability. On epithelial cells the protease facilitates migration in a wound closure assay but does not affect transepithelial leukocyte migration. Blood leukocytes and bone marrow-derived macrophages (BMDM) from ADAM8-deficient mice show suppressed chemotactic response. Intranasal application of LPS to mice is accompanied with ADAM8 upregulation in the lung. In this model of acute lung inflammation ADAM8-deficient mice are protected against leukocyte infiltration. Finally, transfer experiments of BMDM in mice indicate that ADAM8 exerts a promigratory function predominantly on leukocytes. Our study provides in vitro and in vivo evidence that ADAM8 on leukocytes holds a proinflammatory function in acute lung inflammation by promoting alveolar leukocyte recruitment. |
| Databáze: | OpenAIRE |
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