Effects of dexamethasone and indomethacin on elastase, α1-proteinase inhibitor, and fibronectin in bronchoalveolar lavage fluid from neonates

Gerdes, Jeffrey S.; Harris, Mary C.; Polin, Richard A.

doi:10.1016/s0022-3476(88)80390-1

Cited by 73 publications

(27 citation statements)

References 22 publications

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“…Our findings differ from other studies with neonates, that detected free elastase in most or all of the aspirates examined [4][5][6][13][14][15][16]. The explanation may lie in the assays used.…”

Section: Discussioncontrasting

confidence: 99%

“…Another difference is that we measured activities against neutrophil elastase with a substrate designed for the neutrophil enzyme, whereas others [4][5][6][13][14][15] have used pancreatic elastase or its substrate. Pancreatic elastase differs substantially in its reactivity, and does not give absolute activities or inhibitory capacities for the neutrophil enzyme [22].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have measured elastase activity in tracheal aspirates from intubated neonates [4][5][6][13][14][15][16]. When related to total α 1 -PI levels, elastase activity remained high in infants who developed BPD [4,5], it was increased in association with prolonged hyperoxia or infection [6], but there was no sustained elevation in infants treated with surfactant.…”

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confidence: 99%

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Proteinase-antiproteinase balance in tracheal aspirates from neonates

Sluis

Darlow²,

Vissers³

et al. 1994

Eur Respir J

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P Pr ro ot te ei in na as se e--a an nt ti ip pr ro ot te ei in na as se e b ba al la an nc ce e i in n t tr ra ac ch he ea al l a as sp pi ir ra at te es s f fr ro om m n ne eo on na at te es s Activities of neutrophil elastase and its inhibitors were measured in tracheal aspirates from 17 infants, 10 of whom subsequently developed bronchopulmonary dysplasia.All aspirates contained immunologically detectable α 1 -proteinase inhibitor (α 1 -PI), but their inhibitory capacity against neutrophil elastase ranged from being undetectable to being in excess of the amount of α 1 -PI detected immunologically. When the α 1 -PI was removed from each of the aspirates, using a specific antibody, from 0-50% of the original activity remained, indicating the presence of another elastase inhibitor. Its properties were consistent with it being the low molecular mass, secretory leucoproteinase inhibitor (SLPI), also known as bronchial antileucoproteinase. The α 1 -PI was from 0-100% active. Most of the inactive inhibitor was shown by western blotting to be complexed with elastase, with a small amount of cleaved material. There was no evidence of major oxidative inactivation. Free elastase was detected in only three of the aspirates; these had little or no detectable elastase inhibitory capacity, and most of their α 1 -PI was complexed. Elastase load, comprising the sum of free and complexed elastase, correlated closely with myeloperoxidase activity, a recognized marker of inflammatory activity. Active SLPI levels showed a positive correlation with gestational age (r=0.66).We conclude that most neutrophil elastase in the upper airways of ventilated infants is complexed. This indicates that lung secretions of most infants contain adequate inhibitory activity of α 1 -PI and probably secretory leucoproteinase inhibitor.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Proteinase-antiproteinase balance in tracheal aspirates from neonates

Sluis

Darlow²,

Vissers³

et al. 1994

Eur Respir J

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“…Fibronectin is increased in bronchoalveolar lavage both in adults with fibrotic pulmonary disorders, and in infants with BPD (Rennard and Crystal 1981;Gerdes et al 1988). Probably tenascin-C would be increased in ELF and, clinically more importantly, also in serum in patients with BPD.…”

Section: Discussionmentioning

confidence: 99%

Tenascin-C Is Highly Expressed in Respiratory Distress Syndrome and Bronchopulmonary Dysplasia

Kaarteenaho‐Wiik

Kinnula

Soini

et al. 2002

J Histochem Cytochem.

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S U M M A R YTenascin-C is an extracellular matrix (ECM) glycoprotein expressed in human tissues during organogenesis and in fibrotic and neoplastic processes. We hypothesized that its expression would increase in human lung in neonatal disorders such as infant respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). Tenascin-C expression was studied by immunohistochemistry (IHC) and mRNA in situ hybridization (ISH). The extent of tenascin-C immunoreactivity was scored as absent (0), low ( ϩ ), moderate ( ϩϩ ), strong ( ϩϩϩ ), or very strong ( ϩϩϩϩ ) separately in different types of pulmonary cells in controls (seven cases), RDS (19 cases), and BPD (12 cases). In controls, tenascin-C expression was low ( ϩ ) underneath alveolar and bronchiolar epithelium, moderate ( ϩϩ ) in intima of veins, and strong ( ϩϩϩ ) around chondrocytes. In RDS, tenascin-C expression was moderate ( ϩϩ ) or strong ( ϩϩϩ ) underneath both bronchiolar and often detached alveolar epithelium underlying hyaline membranes in the walls of dilated alveoli. In particular, the patients with RDS who survived for 1 day or more had strong expression of tenascin-C within alveolar walls. In patients with BPD, tenascin-C was very strongly ( ϩϩϩϩ ) expressed in the remodeled fibrotic alveolar walls underneath regenerative epithelium. Increased expression of tenascin-C mRNA was seen below the alveolar and bronchiolar epithelia in RDS and BPD. The cells in these locations showed ␣ -smooth muscle actin immunoreactivity, suggesting a myofibroblast phenotype. In conclusion, tenascin-C is highly expressed in the walls of alveoli and bronchioli in RDS and BPD, suggesting an association between the expression of this protein and the presence of these disorders.

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“…These include an increase in surfactant synthesis (12,13) and in activity of antioxidant enzymes (14) shown after prenatal glucocorticoid therapy in fetal animals, and reduction of pulmonary edema, lung water, and alveolar epithelial permeability shown in preterm infants with CLD (5,6,15). DEX may additionally decrease pulmonary inflammation, suggested by reduction of neutrophil recruitment into the lungs (5,16), and decrease bronchoalveolar lavage fluid concentrations of elastase (5,16,17). However, the precise mechanism of action of DEX in ventilator-dependent, small, preterm infants is not known.…”

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confidence: 99%

Dexamethasone Treatment of Infants at Risk for Chronic Lung Disease: Surfactant Components and Inflammatory Parameters in Airway Specimens

et al. 1994

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The mechanisms explaining the beneficial effects of glucocorticoid in ventilator-dependent preterm infants are not known. In the present randomized trial, we evaluated the hypothesis that dexamethasone (DEX) treatment of small, preterm infants at risk for chronic lung disease favorably affects the surfactant system. Twenty-three ventilatordependent infants, with a mean +. SD gestational age of 26 ? 2 wk and a mean birth weight of 836 4 173 g, received 1 wk of treatment with either DEX (dose 0.5 mg/kg/d) or placebo beginning at 2 wk of age. The airway specimens were analyzed for surfactant components, surface activity, surfactant inhibitors, and inflammatory mediators. The concentrations of these parameters in epithelial lining fluid were calculated using the urea method. DEX treatment decreased the concentration of nonsedimentable protein in epithelial lining fluid within 3 d (p < 0.05). The nonsedimentable fraction of airway specimens decreased the surface activity of surfactant as a function of protein concentration. At a constant protein concentration, the protein from placebo-treated infants inhibited the surface activity of human surfactant in vitro more than protein from DEXtreated infants ( p < 0.05). DEX transiently increased the concentration of surfactant protein-A in epithelial lining fluid but had no effect on surface activity of the sedimentable surfactant complex or on concentrations of phosphatidylcholine, IL-1P, lactoferrin, or myeloperoxidase. We conclude that the acute beneficial effect of DEX treatment in preterm ventilator-dependent infants may in part be mediated through a decrease in the concentration of nonsedimentable protein and a decrease in the capacity of this protein to inhibit surface activity. (Pediatr Res 36: 387-393, 1994) Abbreviations AS, airway specimen CLD, chronic lung disease DEX, dexamethasone ELF, epithelial lining fluid LF, lactoferrin MPO, myeloperoxidase PC, phosphatidylcholine PL, placebo SP-A, surfactant protein-A SPC, disaturated phosphatidylcholine Despite improved survival, many preterm infants fail to recover from the acute lung injury and develop CLD. In addition to immaturity, factors contributing to the development of CLD include barotrauma, oxygen toxicity, and inflammation (1, 2). The significance of the various suggested pathogenetic mechanisms is unclear.DEX therapy decreases the requirement of respiratory support and improves pulmonary mechanics in ventilator-dependent preterm infants (3-6). In several controlled trials on ventilator-dependent very-low-birth-weight infants, DEX therapy has improved the short-term pulmonary outcome, decreasing the duration of mechanical ventilation, but not the long-term outcome (7-11). Many potential mechanisms for the acute effect of DEX have been proposed. These include an increase in surfactant synthesis (12, 13) and in activity of antioxidant enzymes (14) shown after prenatal glucocorticoid therapy in fetal animals, and reduction of pulmonary edema, lung water, and alveolar epithelial permeability shown in preterm...

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Effects of dexamethasone and indomethacin on elastase, α1-proteinase inhibitor, and fibronectin in bronchoalveolar lavage fluid from neonates

Cited by 73 publications

References 22 publications

Proteinase-antiproteinase balance in tracheal aspirates from neonates

Proteinase-antiproteinase balance in tracheal aspirates from neonates

Tenascin-C Is Highly Expressed in Respiratory Distress Syndrome and Bronchopulmonary Dysplasia

Dexamethasone Treatment of Infants at Risk for Chronic Lung Disease: Surfactant Components and Inflammatory Parameters in Airway Specimens

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