KL4-surfactant prevents hyperoxic and LPS-induced lung injury in mice

Paul Kinniry, Jeremy Pick, Scott Stephens, Deepika Jain, Charalambos C. Solomides, Ralph Niven, Robert Segal, Melpo Christofidou-Solomidou

Research output: Contribution to journalArticlepeer-review

Abstract

KL4-surfactant contains the novel KL4 peptide, sinapultide, which mimics properties of the hydrophobic pulmonary surfactant protein SP-B, in a phospholipid formulation and may be lung protective in experimental acute respiratory distress syndrome/acute lung injury. Our objective was to determine the protective role of airway delivery of KL 4-surfactant in murine models of hyperoxic and lipopolysaccharide (LPS)-induced lung injury and further explore the mechanisms of protection. For the hyperoxic injury model, mice exposed to 80% O2 for 6 days received an intranasal bolus of vehicle, beractant, or KL4-surfactant on days 3, 4, 5, and 6 of the exposure, and lungs were evaluated on day 7. Mice in the LPS-induced lung injury model received an intratracheal bolus of LPS followed by an intranasal bolus of KL4-surfactant or control at 1, 3, and 19 hr post-LPS challenge, and lungs were evaluated after 24 hr. To explore the mechanisms of protection, in vitro assays were performed with human and murine endothelial cell monolayers, and polymorphonuclear leukocyte (PMN) transmigration in the presence or absence of KL4-surfactant or lipid controls was evaluated. Based on morphology, histopathology white blood cell count, percentage of PMNs, and protein concentration in bronchoalveolar lavage fluid, our data showed KL4-surfactant, unlike vehicle or beractant, blocked neutrophil influx into alveoli and suppressed lung injury. Furthermore, in vitro assays showed KL4-surfactant decreased neutrophil transmigration at the endothelial cell level. KL4-surfactant decreased inflammation and lung permeability compared with controls in both mouse models of lung injury. Evidence suggests the anti-inflammatory mechanism of the KL4-peptide is through inhibition of PMN transmigration through the endothelium.

Original languageEnglish (US)
Pages (from-to)916-928
Number of pages13
JournalPediatric pulmonology
Volume41
Issue number10
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

Keywords

  • Acute lung injury
  • Acute respiratory distress syndrome
  • Mouse model
  • Neutrophil transmigration
  • Protein-containing synthetic surfactant
  • Pulmonary inflammation
  • Surfactant replacement therapy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

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