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Meera Subramaniam, MD

Assistant Professor, Department of Pediatrics, Harvard Medical School

Assistant Professor, Medicine, Boston Children's Hospital

Contact Info

Meera Subramaniam
Boston Children's Hospital
Division of Respiratory Diseases

Boston, MA, 02115
Mailstop: Enders 470
Phone: 617-355-8256
meera.subramaniam@childrens.harvard.edu

Assistant

Not Available.

DF/HCC Program Affiliation

Lung Cancer
Angiogenesis, Invasion and Metastasis

Research Abstract

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.

Publications

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