Endogenous beta-adrenergic receptors inhibit lipopolysaccharide-induced pulmonary cytokine release and coagulation.

Abstract

Beta2-adrenergic receptors are expressed on different cell types in the lung, including respiratory epithelial cells, smooth muscle cells, and macrophages. The aim of the current study was to determine the role of beta-adrenergic receptors in the regulation of lung inflammation induced by instillation via the airways of lipopolysaccharide (LPS) (a constituent of the gram-negative bacterial cell wall) or lipoteichoic acid (LTA) (a component of the gram-positive bacterial cell wall). Mice inhaled the beta-adrenergic antagonist propranolol or saline 30 minutes before and 3 hours after intranasal LPS or LTA administration. LPS and LTA induced a profound inflammatory response in the lungs as reflected by an influx of neutrophils and the release of proinflammatory cytokines and chemokines into bronchoalveolar lavage fluid (BALF). Propranolol inhalation resulted in enhanced LPS-induced lung inflammation, which was reflected by a stronger secretion of TNF-alpha, IL-6, and monocyte chemoattractant protein-1 into BALF and by enhanced coagulation activation (thrombin-antithrombin complexes). In LTA-induced lung inflammation, propranolol did not influence cytokine release but potentiated activation of coagulation. Propranolol did not alter neutrophil recruitment in either model. This study suggests that beta-adrenergic receptors, which are widely expressed in the lungs, serve as negative regulators of pulmonary cytokine release and coagulation induced by LPS and less so during LTA-induced pulmonary inflammation.

• Authors: Ida A J Giebelen, Masja Leendertse, Mark C Dessing, Joost C M Meijers, Marcel Levi, Christian Draing, Sonja von Aulock, Tom van der Poll
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 39 Issue 3 Pg. 373-9 (Sep 2008) ISSN: 1535-4989 [Electronic] United States
• PMID: 18421015 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-2 Receptor Agonists
• Adrenergic beta-2 Receptor Antagonists
• Adrenergic beta-Antagonists
• Cytokines
• Lipopolysaccharides
• Receptors, Adrenergic, beta-2
• Teichoic Acids
• lipoteichoic acid
• Propranolol

Topics

• Administration, Inhalation
• Adrenergic beta-2 Receptor Agonists
• Adrenergic beta-2 Receptor Antagonists
• Adrenergic beta-Antagonists (administration & dosage, pharmacology)
• Animals
• Blood Coagulation (drug effects)
• Bronchoalveolar Lavage Fluid
• Cytokines (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Female
• Lipopolysaccharides (immunology, toxicity)
• Lung (drug effects, immunology)
• Mice
• Mice, Inbred C57BL
• Neutrophils (drug effects)
• Pneumonia, Bacterial (immunology)
• Propranolol (administration & dosage, pharmacology)
• Receptors, Adrenergic, beta-2 (physiology)
• Teichoic Acids (immunology, toxicity)