| First Author | Khatwa UA | Year | 2010 |
| Journal | J Leukoc Biol | Volume | 87 |
| Issue | 1 | Pages | 69-77 |
| PubMed ID | 19801498 | Mgi Jnum | J:155984 |
| Mgi Id | MGI:4418423 | Doi | 10.1189/jlb.0509361 |
| Citation | Khatwa UA, et al. (2010) MMP-8 promotes polymorphonuclear cell migration through collagen barriers in obliterative bronchiolitis. J Leukoc Biol 87(1):69-77 |
| abstractText | Increased levels of MMP-8 (neutrophil collagenase) have been reported in OB, but the biological role of MMP-8 in OB is not known. MMP-8 is an interstitial collagenase highly expressed by polymorphonuclear leukocytes, which are prominent in early OB. Here, we show that MMP-8 promotes migration of PMNs through the collagen-rich matrix in a mouse heterotopic airway transplant model of OB. Overall, MMP-8(-/-) mice had significantly fewer PMNs in the airway lumen 2 and 14 days post-transplantation, and the percentage of PMNs traversing the matrix to the lumen was decreased markedly in the MMP-8(-/-) compared with WT mice at 14 days. There were significantly more PMNs outside of the lumen in the ECM in the MMP-8(-/-) mice compared with WT mice. In vitro, significantly fewer MMP-8(-/-) PMNs migrated through 3D cross-linked collagen gels than WT PMNs. MMP inhibitor GM6001 was also able to impede migration of WT PMNs through collagen gels. The decreased migration was likely a result of pericollagenase activity of MMP-8, as WT PMNs expressing MMP-8 were not able to migrate effectively through collagen that was resistant to the collagenase. Protection from OB was seen in the MMP-8(-/-) mice, as the airway lumen had significantly less obliteration and collagen deposition, suggesting that MMP-8 plays an important role in the pathogenesis of OB. |
