Secretory leukocyte protease inhibitor and lung inflammation in developing bronchopulmonary dysplasia

Watterberg, Kristi L.; Carmichael, David F.; Gerdes, Jeffrey S.; S, Werner; Backstrom, Conra; Murphy, Shirley

doi:10.1016/s0022-3476(94)70209-8

Cited by 80 publications

(41 citation statements)

References 19 publications

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“…Premature newborn infants often require high ventilatory pressure and hyperoxia for resuscitation, a process that induces lung injury and that may contribute to acute and chronic lung disease (15,24) regardless of routine treatment with surfactant (25). The causes and mechanisms of ventilation-induced lung injury have been studied in adult animal models and are believed to be initiated primarily by alveolar macrophages (26).…”

Section: Discussionmentioning

confidence: 99%

“…NE is a potent serine proteinase, responsible for tissue destruction in adult lung with emphysema (36). In the preterm newborn lung, increased NE activity affects lung remodeling and increases alveolar epithelial apoptosis and the development of BPD (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…Total inflammatory cell numbers as well as neutrophils were significantly decreased by rhSP-D ( Figure 4A). Increased NE activity has been associated with development of BPD (15,16). The addition of rhSP-D to Survanta decreased NE activity in the lung ( Figure 4B).…”

Section: Rhsp-d Treatment Decreased Pulmonary Inflammationmentioning

confidence: 93%

“…After the thorax was opened, the deflation limb of pressure-volume curve was measured (5,7). Lung tissue of the right lower lobe was frozen in liquid nitrogen for RNA isolation and measurement of neutrophil elastase (NE) activity (14,15). NE activity was assessed by a spectrophotometric assay using chromogenic substrate specific for NE: N-methoxy-succinyl-Ala-Ala-Pro-Val pNA (16 Lung tissue of the right middle lobe was homogenized in 0.9% NaCl and supernatant after centrifugation at 1,000 3 g for 15 minutes was frozen for ELISA of proinflammatory cytokine proteins (5,7).…”

Section: Methodsmentioning

confidence: 99%

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Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Sato¹,

Whitsett²,

Scheule³

et al. 2010

Am J Respir Crit Care Med

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Rationale: Premature newborns frequently require manual ventilation for resuscitation during which lung injury occurs. Although surfactant protein (SP)-D regulates pulmonary inflammation, SP-D levels are low in the preterm lung. Commercial surfactants for treatment of respiratory distress syndrome do not contain SP-D. Objectives: To determine whether addition of recombinant human SP-D (rhSP-D) to commercial surfactant influences lung inflammation in ventilated premature newborn lambs. Methods: Prematurely delivered lambs (130 d gestation age) were resuscitated with 100% O 2 and peak inspiratory pressure 40 cm H 2 O for 20 minutes and then treated with Survanta or Survanta containing rhSP-D. Ventilation was then changed to regulate tidal volume at 8 to 9 ml/kg. At 5 hours of age lambs were killed for sample collection. Measurements and Main Results: Sequential blood gas and tidal volume were similar in lambs treated with or without rhSP-D, indicating that lung immaturity and ventilatory stress used to support premature lambs were comparable between the two groups. Ventilation caused pulmonary inflammation in lambs treated with surfactant alone. In contrast, surfactant containing rhSP-D decreased neutrophil numbers in bronchoalveolar lavage fluid and decreased neutrophil elastase activity in lung tissue. IL-8 mRNA and IL-8 protein were significantly decreased in the 1rhSP-D group lamb lungs, to 20% of those in controls. The addition of rhSP-D also rendered Survanta more resistant to plasma protein inhibition of surfactant function. Conclusions: Treatment with rhSP-D-containing surfactant inhibited lung inflammation and enhanced the resistance of surfactant to inhibition, supporting its potential usefulness for prevention of lung injury in the preterm newborn.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Rhsp-d Treatment Decreased Pulmonary Inflammationmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Sato¹,

Whitsett²,

Scheule³

et al. 2010

Am J Respir Crit Care Med

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show abstract

“…32 In addition to a1AT, low molecular mass inhibitor secretory leukocyte peptidase inhibitor (SLPI) was found to be important in neutralizing NE in tracheal aspirates of infants born prematurely. 33 Watterberg et al 34 found that SLPI increases in the tracheal lavage of RDS, whereas neonates going on to develop BPD had a significantly higher elastase to elastase-inhibitor ratio. Sveger et al 35 also reported significant correlations with BPD development and low levels of inhibitors a1AT and ACT (SERPINA3) in tracheobronchial aspirate of preterm infants at 3 to 4 days of age, and low SLPI at 7 to 8 days of age.…”

Section: -22mentioning

confidence: 99%

Intracellular and extracellular serpins modulate lung disease

Askew

Silverman

2008

J Perinatol

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An imbalance between peptidases and their inhibitors leads to pulmonary disease. Imbalances occur in the adult and the neonate at risk for a specific set of lung pathologies. Serpins (serine peptidase inhibitors) make up the major source of antipeptidase activity in the lung. The purpose of this review is to describe the serpin mechanism of inhibition, their roles in the normal and pathological lung and their potential as therapeutic agents.

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Bronchopulmonary dysplasia: Pre- and postnatal influences and outcome

Hislop¹

1997

Pediatr. Pulmonol.

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Secretory leukocyte protease inhibitor and lung inflammation in developing bronchopulmonary dysplasia

Cited by 80 publications

References 19 publications

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Surfactant Protein-D Inhibits Lung Inflammation Caused by Ventilation in Premature Newborn Lambs

Intracellular and extracellular serpins modulate lung disease

Bronchopulmonary dysplasia: Pre- and postnatal influences and outcome

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