Oxidative stress and increased type-IV collagenase levels in bronchoalveolar lavage fluid from newborn babies

Oxidative stress may increase lung permeability by upregulation of matrix-m etalloproteinase-9 (MMP-8), a type-IV collagenase that can disrupt alveolar basement membranes. We have compared a marker of oxidative stress (protein carbonyl residues) with levels of MMP-8 and its inhibitor, tissue inhibito r of metalloproteinase-1 (TIMP-1), in bronchoalveolar lavage samples from n ewborn babies. Bronchoalveolar lavage samples (n = 87, two from each time p oint) were taken in the first 6 postnatal days from 41 ventilated babies: 1 8 of <29 wk gestation, 10 of 29-36 wk, 9 term with persistent fetal circula tion, and 4 term without lung disease. Respiratory disease severity at the time of bronchoalveolar lavage was assessed using the arterial-alveolar oxy gen tension ratio. One sample from each time point was used for the measure ment of MMP-9 by zymography and TIMP-1 by ELISA. The second sample was used to measure carbonyl group concentrations, also using an ELISA. Correlation s were calculated between protein carbonyls, arterial-alveolar oxygen tensi on ratio, and MMP-9 and TIMP-1 concentrations, Significant correlations wer e found between carbonyl concentrations and arterial-alveolar oxygen tensio n ratio (r = -0.325, p = 0.0031, n = 81), MMP-9 (r = 0.331, p < 0.0029, n = 79), and TIMP-1 (r = 0.436, p < 0.0001, n = 87). Worsening respiratory dis ease in newborn babies is associated with increased carbonyl concentrations in neonatal bronchoalveolar lavage fluid, and these correlated with MMP-9 and TIMP-1 levels. Increased oxidative stress may damage the lung by increa sing type-IV collagenase activity, causing disruption of the extracellular matrix.