title: Anionic pulmonary surfactant phospholipids inhibit inflammatory responses from alveolar macrophages and U937 cells by binding the lipopolysaccharide-interacting proteins CD14 and MD-2.
abstract: Lipopolysaccharide (LPS), derived from Gram-negative bacteria, is a major cause of acute lung injury and respiratory distress syndrome. Pulmonary surfactant is secreted as a complex mixture of lipids and proteins onto the alveolar surface of the lung. Surfactant phospholipids are essential in reducing surface tension at the air-liquid interface and preventing alveolar collapse at the end of the respiratory cycle. In the present study, we determined that palmitoyl-oleoyl-phosphatidylglycerol and phosphatidylinositol, which are minor components of pulmonary surfactant, and synthetic dimyristoylphosphatidylglycerol regulated the inflammatory response of alveolar macrophages. The anionic lipids significantly inhibited LPS-induced nitric oxide and tumor necrosis factor-alpha production from rat and human alveolar macrophages and a U937 cell line by reducing the LPS-elicited phosphorylation of multiple intracellular protein kinases. The anionic lipids were also effective at attenuating inflammation when administered intratracheally to mice challenged with LPS. Binding studies revealed high affinity interactions between the palmitoyl-oleoyl-phosphatidylglycerol and the Toll-like receptor 4-interacting proteins CD14 and MD-2. Our data clearly identify important anti-inflammatory properties of the minor surfactant phospholipids at the environmental interface of the lung.
authors: Department of Medicine, Program in Cell Biology, National Jewish Health, Denver, Colorado 80206, USA.
authors: Koji
authors: K
authors: Kuronuma
authors: Hiroaki
authors: H
authors: Mitsuzawa
authors: Katsuyuki
authors: K
authors: Takeda
authors: Chiaki
authors: C
authors: Nishitani
authors: Edward D
authors: ED
authors: Chan
authors: Yoshio
authors: Y
authors: Kuroki
authors: Mari
authors: M
authors: Nakamura
authors: Dennis R
authors: DR
authors: Voelker
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000378:metabolism; D051218:Lymphocyte Antigen 96 / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D020298:U937 Cells
chemical_list: C495377:LY96 protein, human; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D010743:Phospholipids; D011663:Pulmonary Surfactants; C495345:TLR4 protein, human; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide