alpha-Galactosylceramide, a ligand of natural killer T cells, inhibits allergic airway inflammation.

Abstract

alpha-Galactosylceramide (alpha-GalCer) is a specific ligand of natural killer T cells (NKT cells) that regulates the immune responses such as tumor rejection and autoimmunity by producing interferon (IFN)-gamma and interleukin (IL)-4. However, it has not been determined whether alpha-GalCer-activated NKT cells modulate allergic inflammation. Because alpha-GalCer induces a large amount of IFN-gamma production by NKT cells, we hypothesized that an in vivo administration of alpha-GalCer could inhibit allergic airway inflammation in mice. Strikingly, a single intraperitoneal injection of alpha-GalCer almost completely abrogated an infiltrate with eosinophils in the lung tissue as well as in the bronchoalveolar lavage. This inhibition of allergic inflammation was associated with a significant decrease in the levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and in the number of goblet cells. In addition, this ligand significantly inhibited airway hyperresponsiveness to inhaled methacholine and raised the serum levels of ovalbumin-specific IgG2a with a decrease in those of ovalbumin-specific IgE. In IFN-gamma knockout mice, however, alpha-GalCer failed to exert such inhibitory effects in this asthma model. These results indicate that alpha-GalCer prevents allergic airway inflammation possibly through IFN-gamma production by ligand-activated NKT cells, suggesting the potential therapeutic application of alpha-GalCer in asthma.

• Authors: Hiroyuki Matsuda, Takafumi Suda, Jun Sato, Toshi Nagata, Yukio Koide, Kingo Chida, Hirotoshi Nakamura
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 33 Issue 1 Pg. 22-31 (Jul 2005) ISSN: 1044-1549 [Print] United States
• PMID: 15802553 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens
• Galactosylceramides
• Immunoglobulin G
• Ligands
• alpha-galactosylceramide
• Immunoglobulin E
• Interferon-gamma
• Ovalbumin

Topics

• Animals
• Antigens (chemistry)
• Asthma (pathology)
• Bronchoalveolar Lavage Fluid
• Cytotoxicity, Immunologic (immunology)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Galactosylceramides (physiology)
• Goblet Cells (pathology)
• Hyperplasia
• Hypersensitivity
• Immunoglobulin E (metabolism)
• Immunoglobulin G (immunology)
• Inflammation
• Interferon-gamma (genetics, metabolism)
• Killer Cells, Natural (cytology)
• Ligands
• Lung (pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Ovalbumin (metabolism)
• T-Lymphocytes (cytology)
• Th2 Cells
• Time Factors