KL4-surfactant prevents hyperoxic and LPS-induced lung injury in mice.
Publication/Presentation Date
10-1-2006
Abstract
KL(4)-surfactant contains the novel KL(4) 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% O(2) for 6 days received an intranasal bolus of vehicle, beractant, or KL(4)-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 KL(4)-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 KL(4)-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 KL(4)-surfactant, unlike vehicle or beractant, blocked neutrophil influx into alveoli and suppressed lung injury. Furthermore, in vitro assays showed KL(4)-surfactant decreased neutrophil transmigration at the endothelial cell level. KL(4)-surfactant decreased inflammation and lung permeability compared with controls in both mouse models of lung injury. Evidence suggests the anti-inflammatory mechanism of the KL(4)-peptide is through inhibition of PMN transmigration through the endothelium.
Volume
41
Issue
10
First Page
916
Last Page
928
ISSN
8755-6863
Published In/Presented At
Kinniry, P., Pick, J., Stephens, S., Jain, D., Solomides, C. C., Niven, R., Segal, R., & Christofidou-Solomidou, M. (2006). KL4-surfactant prevents hyperoxic and LPS-induced lung injury in mice. Pediatric pulmonology, 41(10), 916–928. https://doi.org/10.1002/ppul.20468
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
16871629
Department(s)
Administration and Leadership
Document Type
Article