The effect of water-soluble chitosan on macrophage activation and the attenuation of mite allergen-induced airway inflammation

• Published in: Biomaterials Vol. 29; no. 14; pp. 2173 - 2182
• Main Authors: Chen, Chin-Lung, Wang, Yu-Ming, Liu, Chia-Fang, Wang, Jiu-Yao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.05.2008
• Subjects: Advanced Basic Science; Allergy; Animals; Antigens, Dermatophagoides; Asthma - immunology; Asthma - pathology; Bronchi - drug effects; Bronchi - immunology; Cell Proliferation; Cells, Cultured; Chitosan; Chitosan - pharmacology; Coculture Techniques; Cytokines - genetics; Cytokines - metabolism; Dentistry; Dermatophagoides; Dermatophagoides farinae; Dermatophagoides farinae - immunology; Enzyme-Linked Immunosorbent Assay; Epithelial Cells - drug effects; Epithelial Cells - pathology; Female; Humans; Inflammation - immunology; Inflammation - metabolism; Macrophage; Macrophage Activation - drug effects; Macrophage Activation - immunology; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - immunology; Macrophages, Alveolar - ultrastructure; Male; Mice; Mice, Inbred BALB C; Pseudopodia - drug effects; Solubility; T-Lymphocytes - physiology; Water - chemistry; peripheral blood mononuclear cells; Allergy; house dust mite; TSLP; protein kinase Cζ; Dermatophagoides farinae; PKCζ; Der p; PBMCs; Dermatophagoides pteronyssinus; inducible nitric oxide synthase; HDM; thymic stromal lymphopoietin; scanning electronic microscopy; Arg I; arginase I; MDM; iNOs; Der f; SEM; Chitosan; monocyte-derived macrophages; Macrophage
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2008.01.023

Abstract Chitin and chitosan have versatile anti-tumor, anti-fungal, and antimicrobial biological properties. Oral intakes and intranasal administration of chitin attenuated allergen-induced airway inflammation in sensitized mice, which may be due to its Th1 adjuvant properties. However, their mechanism of action is not entirely clear. In this report, we demonstrate that water-soluble chitosan (WSC) has specific immunomodulatory effects on dust mite allergen Dermatophagoides farinae (Der f)-stimulated, monocyte-derived macrophages (MDM). These effects include polarizing the cytokine balance towards Th1 cytokines, decreasing the production of the inflammatory cytokines IL-6 and TNF-α, down-regulating CD44 and TLR4 receptor expression, and inhibiting T cell proliferation. Scanning electron microscope (SEM) examination found that WSC reduced the rate of pseudopodia formation in Der f-stimulated MDM from allergic asthma patients. The effect of WSC on allergen-stimulated MDM may be mediated via inhibition of PKCζ phosphorylation and NF-κB pathway activation. In a murine model of asthma, we found that intranasal application of WSC attenuates Der f-induced lung inflammation by reducing infiltration of inflammatory cells, epithelial damage, and goblet cell hyperplasia and markedly decreasing production of Arg I, iNOs, and thymic stromal lymphopoietin (TSLP) in the bronchial epithelium. Therefore, we believe that WSC may provide a new therapeutic modality for allergic asthma.