Endogenous attenuation of allergic lung inflammation by syndecan-1.

Abstract

The airway plays a vital role in allergic lung diseases by responding to inhaled allergens and initiating allergic inflammation. Various proinflammatory functions of the airway epithelium have been identified, but, equally important, anti-inflammatory mechanisms must also exist. We show in this study that syndecan-1, the major heparan sulfate proteoglycan of epithelial cells, attenuates allergic lung inflammation. Our results show that syndecan-1-null mice instilled with allergens exhibit exaggerated airway hyperresponsiveness, glycoprotein hypersecretion, eosinophilia, and lung IL-4 responses. However, administration of purified syndecan-1 ectodomains, but not ectodomain core proteins devoid of heparan sulfate, significantly inhibits these inflammatory responses. Furthermore, syndecan-1 ectodomains are shed into the airway when wild-type mice are intranasally instilled with several biochemically distinct inducers of allergic lung inflammation. Our results also show that syndecan-1 ectodomains bind to the CC chemokines (CCL7, CCL11, and CCL17) implicated in allergic diseases, inhibit CC chemokine-mediated T cell migration, and suppress allergen-induced accumulation of Th2 cells in the lung through their heparan sulfate chains. Together, these findings uncover an endogenous anti-inflammatory mechanism of the airway epithelium where syndecan-1 ectodomains attenuate allergic lung inflammation via suppression of CC chemokine-mediated Th2 cell recruitment to the lung.

• Authors: Jie Xu, Pyong Woo Park, Farrah Kheradmand, David B Corry
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 9 Pg. 5758-65 (May 01 2005) ISSN: 0022-1767 [Print] United States
• PMID: 15843578 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Antigens, Fungal
• Chemokines, CC
• Heparan Sulfate Proteoglycans
• Inflammation Mediators
• Membrane Glycoproteins
• Peptide Fragments
• Proteoglycans
• Sdc1 protein, mouse
• Syndecan-1
• Syndecans
• Interleukin-4
• Ovalbumin

Topics

• Adjuvants, Immunologic (deficiency, genetics, metabolism, physiology)
• Administration, Intranasal
• Amino Acid Sequence
• Animals
• Antigens, Fungal (administration & dosage)
• Aspergillus fumigatus (immunology)
• Cell Migration Inhibition
• Chemokines, CC (antagonists & inhibitors, metabolism)
• Gene Deletion
• Heparan Sulfate Proteoglycans (physiology)
• Inflammation Mediators (metabolism, physiology)
• Interleukin-4 (biosynthesis)
• Lung (immunology, metabolism, pathology)
• Membrane Glycoproteins (deficiency, genetics, metabolism, physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Molecular Sequence Data
• Ovalbumin (administration & dosage)
• Peptide Fragments (metabolism, physiology)
• Protein Binding (immunology)
• Protein Structure, Tertiary
• Proteoglycans (deficiency, genetics, metabolism, physiology)
• Respiratory Hypersensitivity (genetics, immunology, pathology, prevention & control)
• Syndecan-1
• Syndecans
• Th2 Cells (immunology, metabolism, pathology)