Functional and Antigenic Concentrations of Alpha-1-Proteinase Inhibitor after Administration for the Prevention of Chronic Lung Disease of Prematurity

Stiskal, Joseph; Itô, Shinya; Cox, Diane W.; Shennan, Andrew; O’Brien, Karel; Kelly, Edmond; Longley, Teresa Barry; Rabinovitch, Marlene; Dunn, Michael

doi:10.1159/000014153

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…Consistent with the above observations, a randomized clinical trial of ␣ 1 -AT supplementation reduced the incidence of pulmonary hemorrhage but did not affect the incidence of BPD in premature infants with respiratory distress syndrome who had also received surfactant treatment (46). In this trial, the plasma concentrations of ␣ 1 -AT were not significantly different between the placebo and control groups (47) and thus could account for the ineffectiveness of ␣ 1 -AT. Our study as well as the previously published studies (42,49) suggest that low levels of NE in new BPD may have contributed to the lack of a statistically significant clinical benefit from ␣ 1 -AT supplementation.…”

Section: Discussionsupporting

confidence: 78%

SERPINB1 upregulation is associated with in vivo complex formation with neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary dysplasia

Yasumatsu

Altiok

Benarafa³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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Bronchopulmonary dysplasia (BPD) continues to be a major cause of morbidity in premature infants. An imbalance between neutrophil elastase and its inhibitors has been implicated in BPD. Serine protease inhibitor (SERPIN)B1 is an inhibitor of neutrophil proteases, including neutrophil elastase (NE) and cathepsin G (cat G). Recent studies suggest that SERPINB1 could provide protection in the airways by regulating excess protease activity associated with inflammatory lung disorders. In this study, we determined the distribution and ontogeny of SERPINB1 in the baboon lung and characterized the expression of SERPINB1 in baboon models of BPD. SERPINB1 expression was detected in the conducting airway and glandular epithelial cells in addition to neutrophils, macrophages, and mast cells. SERPINB1 mRNA and protein expression increased with advancing gestational age and in the new BPD model. In contrast, SERPINB1 expression levels were decreased in the old BPD model. Furthermore, SERPINB1 was detected as a high-molecular-mass (HMM) complex in lung tissue and bronchoalveolar lavage fluid samples from the BPD group. Analysis of the HMM complex by coimmunoprecipitation showed that these complexes were formed between SERPINB1 and NE or cat G. High-performance liquid chromatography (HPLC) ion trap mass spectrometry verified the presence of SERPINB1 in HMM complexes. Finally, NE activity level was compared between new and old baboon models of BPD and was found to be significantly lower in new BPD. Thus SERPINB1 upregulation in new BPD may be protective by contributing to the regulation of neutrophil proteases NE and cat G.

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Section: Discussionsupporting

confidence: 78%

SERPINB1 upregulation is associated with in vivo complex formation with neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary dysplasia

Yasumatsu

Altiok

Benarafa³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…superoxide dismutase [26,27], protease inhibitors, i.e. alpha-1-proteinase [28,29], as well as current investigation of agents with anti-inflammatory potential, i.e. recombinant human Clara cell 10 kD [30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Tidal Liquid Ventilation in Premature Lambs: Physiologic, Biochemical and Histological Correlates

Cox¹,

Stavis²,

Wolfson³

et al. 2003

Neonatology

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Chronic lung disease in infants continues to be problematic. Tidal liquid ventilation (TLV) improves lung mechanics and provides effective gas exchange. We hypothesized that premature lambs could be supported safely with TLV and evaluated 9 preterm lambs (132 days gestation) on TLV up to 72 h. Results (mean ± SEM): pH 7.36 ± 0.003, Pa_CO2 44 ± 0.34 mm Hg, Pa_O2 170 ± 4.8 mm Hg, compliance = 1.65 ± 0.24 ml/cm H₂O/kg, mean arterial blood pressure = 53 ± 0.08 mm Hg, heart rate = 189 ± 1.5 bpm. Blood perflubron levels were 6.0 ± 0.24 µg/ml over 24 h. Tissue perflubron levels increased from 81 ± 7.0 µg/g at 24 h to 108 ± 15 µg/g at 72 h (p < 0.05). There was a difference in perflubron concentrations as a function of tissue (p < 0.001) that correlated to lipid levels (r² = 0.93, p < 0.01). These data demonstrate that TLV is both safe and effective up to 72 h in premature lambs.

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“…Although the number of patients was small, no statistically significant difference in the incidence of BPD was found between the treated and the placebo group. A subsequent report suggests that a high plasma clearance of α1P1 in the neonate may result in inadequate plasma concentrations [116]. In addition, long-term follow-up studies have not been reported, and thus it is not known whether a "delayed" benefit might have been observed.…”

Section: Antiproteinasesmentioning

confidence: 99%

Lung Injury and Bronchopulmonary Dysplasia in Newborn Infants

Christou

Brodsky

2005

J Intensive Care Med

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Bronchopulmonary dysplasia is the most common morbidity among surviving premature infants. Injury to the developing lung is the result of the interaction between a susceptible host and a number of contributing factors such as mechanical ventilation and infection. The resulting persistent impairment of pulmonary function and need for ongoing therapy are the underlying characteristics of bronchopulmonary dysplasia. Important insights into the pathogenesis of bronchopulmonary dysplasia have led to numerous therapies and preventive approaches. Although significant progress has been made, in order to further affect the incidence and severity of the disease, we need to further study (a) the genetically determined predisposing factors, (b) the relative contribution of the various pathogenetic pathways, and, most important, (c) how to best translate the knowledge gained from these studies into effective clinical approaches.

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Functional and Antigenic Concentrations of Alpha-1-Proteinase Inhibitor after Administration for the Prevention of Chronic Lung Disease of Prematurity

Cited by 6 publications

References 33 publications

SERPINB1 upregulation is associated with in vivo complex formation with neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary dysplasia

SERPINB1 upregulation is associated with in vivo complex formation with neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary dysplasia

Long-Term Tidal Liquid Ventilation in Premature Lambs: Physiologic, Biochemical and Histological Correlates

Lung Injury and Bronchopulmonary Dysplasia in Newborn Infants

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