| First Author | Kearns MT | Year | 2014 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 307 |
| Issue | 1 | Pages | L62-70 |
| PubMed ID | 24838751 | Mgi Jnum | J:221723 |
| Mgi Id | MGI:5641416 | Doi | 10.1152/ajplung.00273.2013 |
| Citation | Kearns MT, et al. (2014) Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation. Am J Physiol Lung Cell Mol Physiol 307(1):L62-70 |
| abstractText | Apoptosis of alveolar macrophages and their subsequent clearance by neighboring phagocytes are necessary steps in the resolution of acute pulmonary inflammation. We have recently identified that activation of the Fas death receptor on the cell surface of macrophages drives macrophage apoptosis. However, the source of the cognate ligand for Fas (FasL) responsible for induction of alveolar macrophage apoptosis is not defined. Given their known role in the resolution of inflammation and ability to induce macrophage apoptosis ex vivo, we hypothesized that T lymphocytes represented a critical source of FasL. To address this hypothesis, C57BL/6J and lymphocyte-deficient (Rag-1(-/-)) mice were exposed to intratracheal lipopolysaccharide to induce pulmonary inflammation. Furthermore, utilizing mice expressing nonfunctional FasL, we adoptively transferred donor lymphocytes into inflamed lymphocyte-deficient mice to characterize the effect of lymphocyte-derived FasL on alveolar macrophage apoptosis in the resolution of inflammation. Herein, evidence is presented that lymphocytes expressing FasL enhance alveolar macrophage apoptosis during the resolution of LPS-induced inflammation. Moreover, lymphocyte induction of alveolar macrophage apoptosis results in contraction of the alveolar macrophage pool, which occurs in a FasL-dependent manner. Specifically, FasL-expressing CD8(+) T lymphocytes potently induce alveolar macrophage apoptosis and contraction of the alveolar macrophage pool. Together, these studies identify a novel role for CD8(+) T lymphocytes in the resolution of acute pulmonary inflammation. |
