Decreased Surfactant Protein-B Expression and Surfactant Dysfunction in a Murine Model of Acute Lung Injury

Abstract

This study examines the relationships between inflammation, surfactant protein (SP) expression, surfactant function, and lung physiology in a murine model of acute lung injury (ALI). 129/J mice received aerosolized endotoxin lipopolysaccharide [LPS] daily for up to 96 h to simulate the cytokine release and acute inflammation of ALI. Lung elastance (E(L)) and resistance, lavage fluid cell counts, cytokine levels, phospholipid and protein content, and surfactant function were measured. Lavage and lung tissue SP content were determined by Western blot and immunohistochemistry, and tissue messenger RNA (mRNA) levels were assessed by Northern blot and in situ hybridization. Tumor necrosis factor-alpha and neutrophil counts in bronchoalveolar lavage fluid increased within 2 h of LPS exposure, followed by increases in total protein, interleukin (IL)-1beta, IL-6, and interferon-gamma. E(L) increased within 24 h of LPS exposure and remained abnormal up to 96 h. SP-B protein and mRNA levels were decreased at 24, 48, and 96 h. By contrast, SP-A protein and mRNA levels and SP-C mRNA levels were not reduced. Surfactant dysfunction occurred coincident with changes in SP-B levels. This study demonstrates that lung dysfunction in mice with LPS-ALI corresponds closely with abnormal surfactant function and reduced SP-B expression.

ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol

“…Lung architecture was assessed in E18.5 embryos that had not respired, or in postnatal day 0 pups that had respired, as described previously (14). To assess airspace morphometry, the mean chord length of the saccule airspaces in five randomly chosen microscopic fields of each sample was measured by a blinded viewer using a Leica DMLB microscope interfaced with Leica Q Win 550 image-analysis software (Leica Microsystems, Inc.).…”

Pepsinogen C Proteolytic Processing of Surfactant Protein B

“…MS/MS experiments were performed with an isolation width of 2 Hz, collision energy of 35, activation Q ϭ 0.25, and an activation time of 30. Peptides that showed a neutral loss of 98, 49.5, or 33.2 daltons were subjected for a further round of sequencing (MS 3 ).…”

“…The absence or deficiency of SP-B, due to developmental, genetic, or acquired disease processes, is associated with high surface tension in the alveolar space resulting in atelectasis, even in the presence of sufficient alveolar phospholipids (1). In animal models selective inactivation of SP-B from instilled monoclonal antibodies (2) in response to acute lung injury (3) or upon inactivation of SP-B gene expression in a conditional transgenic mouse model (4) is associated with poor surfactant biophysical profiles. Even when phospholipid levels were low in surfactant obtained from human patients, correction of phospholipid content alone was not sufficient to restore surfactant function, whereas supplementation with exogenous SP-B rapidly improved surface activity (5).…”

Myricetin attenuates lung inflammation and provides protection against lipopolysaccharide-induced acute lung injury by inhibition of NF-κB pathway in rats

“…Gram-negative bacteria have been recognized as the main cause of this infection. Lipopolysaccharide (LPS), present in the bacterial cell wall is an important virulence factor and is a primary factor known to cause the pulmonary inflammation [3,4]. LPS has been reported to cause ALI through several inflammatory mechanisms [5,6].…”