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.
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MMP-8 promotes polymorphonuclear cell migration through collagen barriers in obliterative bronchiolitis
Khatwa, Umakanth A.; Kleibrink, Bjoern E.; Shapiro, Steven D.; Subramaniam, Meera
Follow Journal of Leukocyte Biology
, Volume 87 (1): 69
Fed of American Socs for Experimental Biology – Jan 1, 2010
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