Meera Subramaniam, MD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 355-8256


meera.subramaniam@childrens.harvard.edu

Meera Subramaniam, MD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Pediatrics, Harvard Medical School
  • Assistant Professor, Medicine, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

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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  • Khatwa UA, Kleibrink BE, Shapiro SD, Subramaniam M. MMP-8 promotes polymorphonuclear cell migration through collagen barriers in obliterative bronchiolitis. J Leukoc Biol 2010; 87:69-77. PubMed
  • Subramaniam M, Bausch C, Twomey A, Andreeva S, Yoder BA, Chang L, Crapo JD, Pierce RA, Cuttitta F, Sunday ME. Bombesin-like peptides modulate alveolarization and angiogenesis in bronchopulmonary dysplasia. Am J Respir Crit Care Med 2007; 176:902-12. PubMed