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• W2080272807 abstract "Background: Neutrophil-derived proteinases (mainly serine proteinases) play an important role in neonatal lung tissue damage. However the exent to which MMPs (92 kD Type IV and 72 kD (Interstitial collagenases) participate in the remodelling of the extracellutar matrix (ECM) is unknown. Intrapulmonary leucocytes (neutrophils and alveolar macrophages) are the main secretors of MMPs gelatinases, induced through a prostaglandin-E2 (PG-E2) dependent pathway involving cyclooxygenase-2 (COX-2) and balanced by the natural tissue inhibitors of MMPs (TIMPs). Aims: 1) To evaluate the gelatinolytic activity of MMPs isoforms and their inhibitors in BAL fluids from mechanically ventilated infants; 2) To study the effect of bacterial lipopolysaccaride (LPS) on MMPs activity and inhibition in conditioned media (CM) of cultured BAL cells, in the presence and absence of Ibuprofen (Ibu) or Dexamethasone (Dex). Methods: BAL samples were obtained from 13 intubated and mechanically ventilated neonates(GA>27 629<4039 gr) age 1-30 days with RDS, perinatal asphyxia, diaphragmatic hernia, BPD) and from 3 pediatric patients with chronic pulmonary disease (dysmotile cilia syndrome, cystic fibrosis). After separation of cellular components from fluid phase (FP) by centrifugation, washed pellets were resuspended in RPMI medium, (supplemented with 0,1% FCS and antibiotics), allowed to adhere to Petri dishes at 37°C and 5% CO2 for 1 hour (to select the monocytic-macrophagic population) and then tested for induction of MMPs and production of PG-E2, under basal condition and after 24 hours of treatment with diluent (PBS) versus LPS (10 mg/ml). +/- 50mM Ibu or 1mM Dex. Radioimmunoassays for PG-E2 quantitation, zymograms and reversezymograms for MMPs gelatinolytic activity and inhibition, were of CM of cultured adherent cells and FPs from BALs. Results: Zymograms performed on samples from FPs and CM of cultured BAL cells, in basal conditions, show an appreciable gelatinolytic activity (mainly type IV collagenase MMP-9), whereas reverse zymograms show less evident bands of inhibition (TIMPs). A marked induction of MMP-9 (more evident in the neonates than in the pediatric patients) and a consistent reduction of TIMPs activity, associated with a 10-100 fold increase of PG-E2 production, were observed after 24 hours of LPS stimulus. The patterns of gelatinolytic activity and inhibition were almost totally reversed in the presence of Ibu, with only minimal changes induced by Dex. Conclusions An imbalance between ECM degradative activity (particularly of MMP-9) and inhibition is observed in FPs and cells from BALs, under basal conditions and after LPS induction. Sub-epithelial basal membrane ECM components (particular type IV collagen) are more susceptible to damage since MMP-9 specifically degrades type IV collagen and can significantly contribute to the sustained increase in pulmonary permeability characteristic of the flogistic reaction that follows acute neonatal lung injury. The role of the MMPs/TIMPs imbalance in the evolution of neonatal lung disease and its possible modulation by acting on the COX-2-mediated PG-E2 inducible synthesis, warrants further studies." @default.
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• W2080272807 title "Imbalance Between Matrix Metalloproteinase (MMPs) and their Inhibitors in BALs of Mechanically Ventilated Neonates † 1704" @default.
• W2080272807 doi "https://doi.org/10.1203/00006450-199804001-01726" @default.
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