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Am J Physiol Lung Cell Mol Physiol 283: L1086-L1093, 2002. First published August 9, 2002; doi:10.1152/ajplung.00066.2002
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Vol. 283, Issue 5, L1086-L1093, November 2002

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

Claude Danan1, Pierre-Henri Jarreau2, Marie-Laure Franco3, Gilles Dassieu1, Christophe Grillon1, Issam Abd Alsamad4, Chantal Lafuma3, Alain Harf3, and Christophe Delacourt3

1 Unité de Réanimation Néonatale and 4 Service d'Anatomopathologie, Centre Hospitalier Intercommunal de Créteil, and 3 Institut National de la Santé et de la Recherche Médicale U492, Faculté de Médecine de Créteil, 94000 Créteil; and 2 Service de Réanimation Néonatale, Hôpital Cochin-Port Royal, 75014 Paris, France

Matrix-degrading metalloproteinases may play a role in the pathophysiology of bronchopulmonary dysplasia (BDP). We, therefore, evaluated correlations between gelatinase activities [metalloproteinase (MMP)-2 and MMP-9] or tissue inhibitor of metalloproteinase (TIMP)-1 levels present in the airways during the initial phase of hyaline membrane disease and the onset of BPD. Tracheal aspirates were obtained within 6 h of birth (day 0) from 64 intubated neonates with a gestational age <= 30 wk. Forty-five neonates were resampled on day 3 or 5. Total MMP-2 level measured by zymography fell with time, whereas total MMP-9 level and TIMP-1 levels, assayed by ELISA, increased; the MMP-9 increase correlated with the increase in airway inflammatory cell numbers. Among the parameters measured on day 0, 3, or 5, lower total MMP-2 level, lower birth weight, and higher fraction of inspired oxygen on day 0 were significantly and independently associated with the development of BPD. In conclusion, MMP-9 level and TIMP-1 levels increased after birth but are not linked to BPD outcome. In contrast, low MMP-2 level at birth is strongly associated with the development of BPD.

metalloproteinase; lung development; newborn; extracellular matrix


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