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Anionic Surfactant Phospholipids Inhibit Lipopolysaccaride‐induced Inflammation from Alveolar Macrophages and U937 Cells
Author(s) -
Kuronuma Koji,
Mitsuzawa Hiroaki,
Takeda Katsuyuki,
Voelker Dennis R
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a59
Subject(s) - chemistry , pulmonary surfactant , lipopolysaccharide , u937 cell , inflammation , tumor necrosis factor alpha , biochemistry , immunology , biology , apoptosis
Lipopolysaccharide (LPS), derived from Gram‐negative bacteria, is a potent pro‐inflammatory toxin and causes lethal disorders including acute lung injury and acute respiratory distress syndrome. Pulmonary surfactant is secreted as a complex mixture of lipids and proteins by alveolar type II cells. Surfactant phospholipids are essential in reducing surface tension at the air‐liquid interface. In the present study, we determined palmitoyloleoyl‐phosphatidylglycerol (POPG) and phosphatidylinositol (PtdIns), which are minor components of surfactant, regulated the inflammatory response of alveolar macrophages. POPG and PtdIns significantly inhibited LPS‐induced nitric oxide and tumor necrosis factor (TNF)‐α production from rat and human alveolar macrophages and U937 cell lines. POPG reduced LPS‐elicited phosphorylation of p38 MAPK , ERK and Iκ Bα and mitogen‐activated protein kinase phosphatase (MKP)‐1 expression. POPG and PtdIns strongly bind to CD14 and appear to block the toll‐like receptor 4 signaling by interfering with direct binding of LPS to CD14. POPG administered intratracheally to mice inhibited the LPS‐induced neutrophil infiltration and TNF‐α production in the pulmonary compartment. POPG was also effective when administered intravenously. Our data clearly identify the anti‐inflammatory properties of surfactant phospholipids at the environmental interface of the lung. NIH PO1‐HL073907.