Craig, VPolverino, FrancescaLaucho-Contreras, Maria E.Shi, YuanyuanLiu, YushiOsorio, Juan C.Tesfaigzi, YohannesPinto-Plata, Victor ManuelGochuico, Bernadette R.Rosas, IvanOwen, Caroline2014-07-072014Craig, V. J., F. Polverino, M. E. Laucho-Contreras, Y. Shi, Y. Liu, J. C. Osorio, Y. Tesfaigzi, et al. 2014. “Mononuclear Phagocytes and Airway Epithelial Cells: Novel Sources of Matrix Metalloproteinase-8 (MMP-8) in Patients with Idiopathic Pulmonary Fibrosis.” PLoS ONE 9 (5): e97485. doi:10.1371/journal.pone.0097485. http://dx.doi.org/10.1371/journal.pone.0097485.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406946Objectives: Matrix metalloproteinase-8 (MMP-8) promotes lung fibrotic responses to bleomycin in mice. Although prior studies reported that MMP-8 levels are increased in plasma and bronchoalveolar lavage fluid (BALF) samples from IPF patients, neither the bioactive forms nor the cellular sources of MMP-8 in idiopathic pulmonary fibrosis (IPF) patients have been identified. It is not known whether MMP-8 expression is dys-regulated in IPF leukocytes or whether MMP-8 plasma levels correlate with IPF outcomes. Our goal was to address these knowledge gaps. Methods: We measured MMP-8 levels and forms in blood and lung samples from IPF patients versus controls using ELISAs, western blotting, and qPCR, and assessed whether MMP-8 plasma levels in 73 IPF patients correlate with rate of lung function decline and mortality. We used immunostaining to localize MMP-8 expression in IPF lungs. We quantified MMP-8 levels and forms in blood leukocytes from IPF patients versus controls. Results: IPF patients have increased BALF, whole lung, and plasma levels of soluble MMP-8 protein. Active MMP-8 is the main form elevated in IPF lungs. MMP-8 mRNA levels are increased in monocytes from IPF patients, but IPF patients and controls have similar levels of MMP-8 in PMNs. Surprisingly, macrophages and airway epithelial cells are the main cells expressing MMP-8 in IPF lungs. Plasma and BALF MMP-8 levels do not correlate with decline in lung function and/or mortality in IPF patients. Conclusion: Blood and lung MMP-8 levels are increased in IPF patients. Active MMP-8 is the main form elevated in IPF lungs. Surprisingly, blood monocytes, lung macrophages, and airway epithelial cells are the main cells in which MMP-8 is upregulated in IPF patients. Plasma and BALF MMP-8 levels are unlikely to serve as a prognostic biomarker for IPF patients. These results provide new information about the expression patterns of MMP-8 in IPF patients.en-USBiology and Life SciencesCell BiologyCellular TypesAnimal CellsImmune CellsImmunologyClinical ImmunologyMedicine and Health SciencesPulmonologyInterstitial Lung DiseasesJournal Article2014-07-0710.1371/journal.pone.0097485