| First Author | Dreymueller D | Year | 2017 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 313 |
| Issue | 3 | Pages | L602-L614 |
| PubMed ID | 28596294 | Mgi Jnum | J:244634 |
| Mgi Id | MGI:5913413 | Doi | 10.1152/ajplung.00444.2016 |
| Citation | Dreymueller D, et al. (2017) The metalloproteinase ADAM8 promotes leukocyte recruitment in vitro and in acute lung inflammation. Am J Physiol Lung Cell Mol Physiol 313(3):L602-L614 |
| abstractText | 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 alphaL-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. |
