title: Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and -2 in different phases of bronchopulmonary dysplasia.
abstract: Bronchopulmonary dysplasia (BPD) can evolve in prematurely born infants who require mechanical ventilation because of hyaline membrane disease (HMD). The development of BPD can be divided in an acute, a regenerative, a transitional, and a chronic phase. During these different phases, extensive remodeling of the lung parenchyma with re-epithelialization of the alveoli and formation of fibrosis occurs. Matrix metalloproteinase-1 (MMP-1) is an enzyme that is involved in re-epithelialization processes, and dysregulation of MMP-1 activity contributes to fibrosis. Localization of MMP-1 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, were investigated in lung tissue obtained from infants who died during different phases of BPD development. In all studied cases (n = 50) type-II pneumocytes were found to be immunoreactive for MMP-1, TIMP-1, and TIMP-2. During the acute and regenerative phase of BPD, type-II pneumocytes re-epithelialize the injured alveoli. This may suggest that MMP-1 and its inhibitors, expressed by type-II pneumocytes, play a role in the re-epithelialization process after acute lung injury. Although MMP-1 staining intensity remained constant in type-II pneumocytes during BPD development, TIMP-1 increased during the chronic fibrotic phase. This relative elevation of TIMP-1 compared with MMP-1 is indicative for reduced collagenolytic activity by type-II pneumocytes in chronic BPD and may contribute to fibrosis. Fibrotic foci in chronic BPD contained fibroblasts immunoreactive for MMP-1 and TIMP-1 and -2. This may indicate that decreased collagen turnover by fibroblasts contributes to fibrosis in BPD development.
authors.affiliation: Department of Immunology, Sophia Children's Hospital, Division of Neonatology, Erasmus University Rotterdam and University Hospital Rotterdam-Dijkzigt, The Netherlands. dik@immu.fgg.eur.nl
authors.forename: W A
authors.initials: WA
authors.lastname: Dik
authors.forename: R R
authors.initials: RR
authors.lastname: De Krijger
authors.forename: L
authors.initials: L
authors.lastname: Bonekamp
authors.forename: B A
authors.initials: BA
authors.lastname: Naber
authors.forename: L J
authors.initials: LJ
authors.lastname: Zimmermann
authors.forename: M A
authors.initials: MA
authors.lastname: Versnel
mesh_terms: D001344:Autopsy; D001997:Bronchopulmonary Dysplasia / Q000201:enzymology / Q000503:physiopathology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007234:Infant, Premature; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020781:Matrix Metalloproteinase 1