crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model

• Published in: Clinical and experimental immunology Vol. 161; no. 2; pp. 233 - 241
• Main Authors: Katoh, S, Maeda, S, Fukuoka, H, Wada, T, Moriya, S, Mori, A, Yamaguchi, K, Senda, S, Miyagi, T
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-08-2010; Blackwell Publishing Ltd; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Antigens; Antigens, Dermatophagoides - immunology; Asthma; Asthma - genetics; Asthma - immunology; Asthma - physiopathology; Azides - pharmacology; Biological and medical sciences; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - physiopathology; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD44; Cell Count; Chemokine CCL11 - metabolism; Chronic obstructive pulmonary disease, asthma; Enzyme Inhibitors - pharmacology; Eosinophils - cytology; Eosinophils - immunology; Female; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Gene Expression - genetics; Gene Expression - immunology; Hyaluronan Receptors - metabolism; Hyaluronic Acid - metabolism; Inflammation - immunology; Inflammation - pathology; Interferon-gamma - metabolism; Interleukins - metabolism; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymphocyte Activation - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, Mutant Strains; Neu1 sialidase; Neuraminidase - antagonists & inhibitors; Neuraminidase - genetics; Neuraminidase - metabolism; Neuraminidase - pharmacology; Peanut Agglutinin - metabolism; Pneumology; Rodents; Sialic Acids - pharmacology; SM/J mice; Spleen - cytology; Spleen - enzymology; Spleen - immunology; Th1 Cells - cytology; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 cells; Th2 Cells - cytology; Th2 Cells - immunology; Th2 Cells - metabolism; Translational Studies; Vaccination; Animal model; SM/J mice; Helper cell; Biochemistry; Respiratory system; Respiratory tract; Bronchus disease; Th2 lymphocyte; Obstructive pulmonary disease; Biological receptor; Transmembrane protein; Lung disease; Enzyme; Respiratory disease; Extractable nuclear antigen; Acute; Rodentia; Cell adhesion molecule; Inflammation; Neu1 sialidase; Th2 cells; Asthma; Glycosylases; Vertebrata; Mammalia; Mouse; Glycosidases; Animal; Exo-α-sialidase; Glycosaminoglycan; Hydrolases; Hyaluronic acid; CD44
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2010.04165.x

CD44 is a highly glycosylated cell adhesion molecule that is involved in lymphocyte infiltration of inflamed tissues. We have demonstrated previously that sialic acid residues of CD44 negatively regulates its receptor function and CD44 plays an important role in the accumulation of T helper type 2 (Th2) cells in the airway of a murine model of acute asthma. Here we evaluated the role of sialidase in the hyaluronic acid (HA) receptor function of CD44 expressed on CD4⁺ T cells, as well as in the development of a mite antigen-induced murine model of acute asthma. Splenic CD4⁺ T cell binding of HA was examined with flow cytometry. Expression of sialidases (Neu1, Neu2, Neu3 and Neu4) in spleen cells was evaluated by quantitative real-time reverse transcription-polymerase chain reaction. Airway inflammation and airway hyperresponsiveness (AHR) were evaluated in the asthmatic Neu1-deficient mouse strain SM/J model. Splenic CD4⁺ T cells from asthmatic model mice displayed increased HA receptor activity of CD44 after culture with the antigen, along with characteristic parallel induction of sialidase (Neu1) expression. This induction of HA binding was suppressed significantly by a sialidase inhibitor and was not observed in SM/J mice. Th2 cytokine concentration and absolute number of Th2 cells in the bronchoalveolar lavage fluid, and AHR were decreased in SM/J mice. In conclusion, HA receptor activity of CD44 and acute asthmatic reactions, including Th2-mediated airway inflammation and AHR, are dependent upon Neu1 enzymatic activity. Our observation suggests that Neu1 may be a target molecule for the treatment of asthma.