Proteinase-antiproteinase balance in tracheal aspirates from neonates

Sluis, K. B.; Darlow, Brian A; Vissers, Margreet C.M.; Winterbourn, C C

doi:10.1183/09031936.94.07020251

Cited by 31 publications

(23 citation statements)

References 23 publications

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“…Cell smears were stained with the standard May-Grü nwaldGiemsa procedure, and differential cell counts were done. This technique was very close to others previously described (15,32). Although some authors used higher aliquot volumes and higher aliquot numbers, those studies were concerned with neonates with higher gestational age and higher birth weight than in our population (9,16).…”

Section: Methodsmentioning

confidence: 56%

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

Danan

Jarreau

Franco

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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2002.-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 Յ30 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 PREMATURE NEONATES WITH HYALINE membrane disease are at risk of developing bronchopulmonary dysplasia (BPD), as a sequel of both the disease and its treatment. The pathogenesis is unclear, but BPD is thought to result from damage to an immature lung. Mechanical ventilation, oxygen therapy, and airway inflammatory responses have all been implicated in the development of BPD (19). These insults appear to interfere with normal lung maturation, which is incomplete at birth. In particular, they appear to alter alveolar formation, on the basis of morphometric studies of severe BPD (3, 24). Alveolar formation is characterized by the multiplication of alveolar septa and the thinning of interalveolar walls, both of which require intense remodeling of the pulmonary extracellular matrix (4). Changes in matrix turnover have been experimentally linked to abnormal alveolar formation (20). The proteinase-antiproteinase balance in the lung is a key factor in harmonious matrix turnover. In particular, matrix metalloproteinases (MMPs), which can synergistically digest the major macromolecules of connective tissue matrices, have been implicated in physiological regulation of lung growth. The MMP gelatinase A (MMP-2) has been shown to play a role in the major collagen turnover that occurs during early postnatal rat lung growth (1, 2). We postulated that MMP-2 might also participate in human lung development and that inadequate MMP-2 levels in premature lungs exposed to insults could contribute to impaired lung growth and thus to BPD. We also postulated that MMPs may be secreted in excess during the inflammatory response associated with hyaline membrane disease and may, therefore, lead to tissue degradation. Gelatinase B (MMP-9) is the main MMP released by inflammatory cells such as neutrophils and alveolar macroph...

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Section: Methodsmentioning

confidence: 56%

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

Danan

Jarreau

Franco

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…However, the potential release of secretory leukocyte protease inhibitor by amnion in vivo may be considerable, due to the large surface area of the amniotic membrane. In addition, it has been previously demonstrated that secretory leukocyte protease inhibitor is present in high concentrations within tracheal aspirates from neonates (Ohlsson et al 1992) with levels correlating positively with gestational age (Sluis et al 1994). Although we have demonstrated that fetal urine contains secretory leukocyte protease inhibitor, it was only detectable in one quarter of all samples tested and therefore unlikely to account for the consistently high levels of secretory Figure 3 Release of secretory leukocyte protease inhibitor by explants of third trimester amnion, chorio-decidua, decidua and placenta maintained in culture for 24 h. Significantly more secretory leukocyte protease inhibitor was released by choriodecidua and decidua than by placenta and amnion.…”

Section: Discussionmentioning

confidence: 99%

Secretory leukocyte protease inhibitor concentration increases in amniotic fluid with the onset of labour in women: characterization of sites of release within the uterus

Denison¹,

Kelly²,

Calder³

et al. 1999

Journal of Endocrinology

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Secretory leukocyte protease inhibitor is a potent inhibitor of neutrophil function, a mediator of mucosal immunity and an inhibitor of NF B regulated inflammatory responses. However, its source, function and regulation within the uterus during pregnancy and at parturition are not well defined. In amniotic fluid, the concentration of secretory leukocyte protease inhibitor increased significantly from 2nd trimester (24 3 ng/ml; mean ...; n=20) to term (751 53 ng/ml; P<0·05; n=15) with a further profound increase (P<0·005) with the onset of labour (3929 1076 ng/ml; n=15). To establish the intrauterine sites of secretion, explants (n=6 different patients per tissue) were collected at term after elective caesarean section. High levels of secretory leukocyte protease inhibitor were released by decidua (135·2 12·4 pg/mg; mean ...) and chorio-decidua (325·1 26·4 pg/mg) with less by amnion (55·6 6·0 pg/mg) and placenta (9·2 1·9 pg/mg). Intense immunoreactivity for secretory leukocyte protease inhibitor was detected predominantly in decidua parietalis cells adherent to the chorion laeve and myometrium, and also in decidua basalis. We propose that, within the pregnant uterus, secretory leukocyte protease inhibitor is released by decidua, fetal membranes and potentially the fetal lung. The increase in secretory leukocyte protease inhibitor may act to modulate proinflammatory paracrine interactions for the maintenance of pregnancy and limit those occurring at parturition within the uterus.

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“…Historically, neutrophil elastase has been linked to elastin degradation in BPD (16). However, in surfactant-treated human and baboon infants with otherwise uncomplicated BPD, free neutrophil elastase levels in the airways are very low or undetectable (17,18). Recently, we have shown up-regulation of several papain-like lysosomal cysteine proteases in a baboon model of BPD (19).…”

mentioning

confidence: 99%

Cathepsin S Deficiency Confers Protection from Neonatal Hyperoxia-induced Lung Injury

Hirakawa

Pierce²,

Bingol-Karakoc³

et al. 2007

Am J Respir Crit Care Med

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Rationale: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that adversely affects long-term pulmonary function as well as neurodevelopmental outcomes of preterm infants. Elastolytic proteases have been implicated in the pathogenesis of BPD. Cathepsin S (cat S) is a cysteine protease with potent elastolytic activity. Increased levels and activity of cat S have been detected in a baboon model of BPD. Objectives: To investigate whether deficiency of cat S alters the course of hyperoxia-induced neonatal lung injury in mice. Methods: Newborn wild-type and cat S-deficient mice were exposed to 80% oxygen for 14 days. Histologic and morphometric analysis were performed and bronchoalveolar lavage protein and cells were analyzed. Lung elastin was assessed by real-time polymerase chain reaction, in situ hybridization, desmosine analysis, and Hart's stain. Distribution of myofibroblasts was analyzed by immunofluorescence. Hydroxyproline content of lung tissues was measured. Measurements and Main Results: Hyperoxia-exposed cat S-deficient mice were protected from growth restriction and had improved alveolarization, decreased septal wall thickness, lower number of macrophages, and lower protein concentration in bronchoalveolar lavage fluid. a-Smooth muscle actin-expressing myofibroblasts accounted for at least some of the increased interstitial cellularity in hyperoxia-exposed mouse lungs and were significantly less in cat S-deficient lungs. Lung hydroxyproline content was increased in hyperoxia-exposed wild-type, but not in cat S-deficient lungs. Desmosine content was significantly reduced in both genotypes with hyperoxia. Conclusions: Cathepsin S deficiency improves alveolarization, and attenuates macrophage influx and fibroproliferative changes in hyperoxia-induced neonatal mouse lung injury.Keywords: cathepsin; bronchopulmonary dysplasia; hyperoxia; myofibroblast Advanced perinatal care over the past decade has resulted in improved survival of very-low-birth-weight (VLBW) (birth weight , 1,500 g) infants (1). However, surviving VLBW infants have increased risk of major morbidities, particularly bronchopulmonary dysplasia (BPD). BPD has a negative impact on not only short-term and long-term pulmonary function but also on overall growth and neurodevelopment of VLBW infants (2-4). The major pathologic findings associated with BPD in surfactant-treated lungs are inflammation, disrupted alveolar development, and variable amounts of fibrosis (5). Exposure of the immature lung to hyperoxia, prolonged mechanical ventilation, and antenatal or postnatal infections are primary risk factors for BPD (6, 7). However, the molecular mechanisms that link these factors to disruption of alveolarization are not completely understood and there are currently no evidence-based strategies to prevent or treat BPD.Several studies have shown that alveolar elastin expressed by myofibroblasts is a critical component of alveolar development (8, 9). The impaired alveolar development in BPD is also accompanied by changes in deposition of elas...

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Proteinase-antiproteinase balance in tracheal aspirates from neonates

Cited by 31 publications

References 23 publications

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

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

Secretory leukocyte protease inhibitor concentration increases in amniotic fluid with the onset of labour in women: characterization of sites of release within the uterus

Cathepsin S Deficiency Confers Protection from Neonatal Hyperoxia-induced Lung Injury

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