| First Author | Fernández FG | Year | 2005 |
| Journal | Am J Transplant | Volume | 5 |
| Issue | 4 Pt 1 | Pages | 671-83 |
| PubMed ID | 15760390 | Mgi Jnum | J:278307 |
| Mgi Id | MGI:6323281 | Doi | 10.1111/j.1600-6143.2005.00751.x |
| Citation | Fernandez FG, et al. (2005) Inhibition of obliterative airway disease development in murine tracheal allografts by matrix metalloproteinase-9 deficiency. Am J Transplant 5(4 Pt 1):671-83 |
| abstractText | This study was designed to define the roles of matrix metalloproteinase (MMP)-2 and MMP-9 in obliterative airway disease (OAD) in heterotopic murine tracheal allografts, considered a suitable animal model for chronic lung allograft rejection. BALB/c tracheal allografts were transplanted into MMP-2-deficient (-/-) and MMP-9-/- mice. Also, wild-type recipients were treated with doxycycline, a nonspecific MMP inhibitor. After 10, 20 and 30 days, allografts were analyzed for OAD development, intragraft levels of MMP-2 and MMP-9 and the frequency and cytokine/chemokine production profile of alloreactive T cells. Allografts transplanted into wild-type mice developed OAD lesions within 30 days. These allografts revealed significant upregulation of both MMP-2 and MMP-9. Allografts transplanted into MMP-9-/- and doxycycline-treated recipients did not develop OAD. In contrast, allografts transplanted into MMP-2-/- mice developed OAD lesions with normal kinetics. Interestingly, MMP-9-/- recipients showed an enhanced T cell alloreactivity associated with an abnormal profile of cytokine/chemokine production. The enhanced T cell alloreactivity in MMP-9-/- mice was mediated by enhanced dendritic cell stimulatory capacity as well as enhanced T cell responsive capacity. These results suggest that MMP-9 plays an important role in the pathogenesis of OAD and may represent a target for the therapeutic intervention of chronic lung allograft rejection. |
