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Pulmonary lipopolysaccharide (LPS)-binding protein inhibits the LPS-induced lung inflammation in vivo.

Abstract
LPS-binding protein (LBP) facilitates the interaction of the Gram-negative cell wall component LPS with CD14, thereby enhancing the immune response to LPS. Although lung epithelial cells have been reported to produce LBP in vitro, knowledge of the in vivo role of pulmonary LBP is limited. Therefore, in the present study we sought to determine the function of pulmonary LBP in lung inflammation induced by intranasal administration of LPS in vivo. Using LBP-deficient (LBP-/-) and normal wild-type mice, we show that the contribution of LBP to pulmonary LPS responsiveness depended entirely on the LPS dose. Although the inflammatory response to low dose (1 ng) LPS was attenuated in LBP-/- mice, neutrophil influx and cytokine/chemokine concentrations in the bronchoalveolar compartment were enhanced in LBP-/- mice treated with higher (>10 ng) LPS doses. This finding was specific for LBP, because the exogenous administration of LBP to LBP-/- mice reversed this phenotype and reduced the local inflammatory response to higher LPS doses. Our results indicate that pulmonary LBP acts as an important modulator of the LPS response in the respiratory tract in vivo. This newly identified function of pulmonary LBP might prove beneficial by enabling a protective immune response to low LPS doses while preventing an overwhelming, potentially harmful immune response to higher doses of LPS.
AuthorsSylvia Knapp, Sandrine Florquin, Douglas T Golenbock, Tom van der Poll
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 176 Issue 5 Pg. 3189-95 (Mar 01 2006) ISSN: 0022-1767 [Print] United States
PMID16493079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Acute-Phase Proteins
  • Carrier Proteins
  • Inflammation Mediators
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • lipopolysaccharide-binding protein
Topics
  • Acute-Phase Proteins (administration & dosage, deficiency, genetics, physiology)
  • Animals
  • Bronchoalveolar Lavage Fluid
  • Carrier Proteins (administration & dosage, genetics, physiology)
  • Cell Line
  • Dose-Response Relationship, Immunologic
  • Female
  • Inflammation Mediators (administration & dosage, physiology)
  • Lipopolysaccharides (administration & dosage, antagonists & inhibitors, metabolism)
  • Lung (immunology, metabolism, pathology)
  • Macrophages, Alveolar (immunology, metabolism, pathology)
  • Membrane Glycoproteins (administration & dosage, deficiency, genetics, physiology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pneumonia (genetics, immunology, prevention & control)

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