| First Author | Gurczynski SJ | Year | 2016 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 311 |
| Issue | 3 | Pages | L611-27 |
| PubMed ID | 27448666 | Mgi Jnum | J:236537 |
| Mgi Id | MGI:5806356 | Doi | 10.1152/ajplung.00193.2016 |
| Citation | Gurczynski SJ, et al. (2016) Loss of CCR2 signaling alters leukocyte recruitment and exacerbates gamma-herpesvirus-induced pneumonitis and fibrosis following bone marrow transplantation. Am J Physiol Lung Cell Mol Physiol 311(3):L611-27 |
| abstractText | CCR2-expressing leukocytes are required for the progression of fibrosis in models of induced lung injury as well as models of bone marrow transplant (BMT)-related idiopathic pneumonia syndrome. Infection with murid gamma-herpesvirus-68 (gammaHV-68) results in severe pneumonitis and pulmonary fibrosis following syngeneic BMT; however, the roles that various proinflammatory leukocyte populations play in this process remain unclear. Deletion of CCR2 in both non-BMT and BMT mice increased early lytic viral replication and resulted in a reduction in the numbers of lung-infiltrating GR1+,F4/80+ and CXCR1+ cells, while maintaining robust neutrophil infiltration. Similarly, in gammaHV-68-infected CCR2(-/-) BMT mice, recruitment of monocytes and lymphocytes were reduced whereas neutrophil recruitment was increased compared with wild-type (WT) BMT mice. Interestingly, levels of profibrotic IL-17 were increased in infected CCR2 BMT mice compared with WT BMT. Furthermore, an increase in lung-associated collagen was detected even though there was an overall decrease in the number of profibrotic CCR2+ fibrocytes detected in the lungs of CCR2(-/-) BMT mice. These data indicate that, contrary to most models of fibrosis, deletion of CCR2 offers no protection from gamma-herpesvirus-induced pneumonitis and fibrosis, and, indeed, CCR2+ cells play a suppressive role during the development of pulmonary fibrosis following gamma-herpesvirus infection post-BMT by limiting IL-7 and collagen production. |
