水溶性壳聚糖激活巨噬细胞，减弱粉尘螨介导的炎症反应

Chen, C.-L., Y.-M. Wang, et al. (2008). "The effect of water-soluble chitosan on macrophage activation and the attenuation of mite allergen-induced airway inflammation." Biomaterials 29(14): 2173-2182.
译者：乔莹
背景介绍：
   “The effect of water-soluble chitosan on macrophage activation and the attenuation of mite allergen-induced airway inflammation”是台湾国立成功大学医学院(College of Medicine, National Cheng Kung University)最新发表在Biomaterials(IF=6.262)上的文章。
    巨噬细胞在过敏反应，像是哮喘、关节炎等中起到重要的作用，该实验室之前的研究发现粉尘螨(Dermatophagoides pteronyssinus)可以在体内外无预先致敏的情况下激活先天性免疫细胞。这种激活可导致肺泡巨噬细胞产生NO，并且是经由CD14/toll-like4受体 (TLR4)。作者较有兴趣想研究水溶性壳聚糖在过敏原刺激过的巨噬细胞中扮演什么样的角色。
他们的研究发现水溶性壳聚糖可以特异性的调控粉尘螨刺激的单核来源的巨噬细胞，通过促进细胞因子的平衡转向Th1细胞因子，降低炎症型细胞因子IL-6和TNF-a,下调CD44 和TLR4 受体的表达并抑制T细胞增殖。扫描电镜发现水溶性壳聚糖可降低粉尘螨刺激的单核来源巨噬细胞伪足的形成。其主要的信号转导机制可能是通过下调PKCζ的磷酸化及抑制NF-kB的活化来实现。
在哮喘的小鼠模型中，作者发现鼻内滴入水溶性壳聚糖可以弱化粉尘螨刺激的肺部炎症反应，降低侵润的炎症细胞数量，降低上皮细胞损伤，降低上皮杯状细胞增生，并且显著降低支气管上皮细胞的Arg I, iNOs和胸腺基质淋巴细胞生成素（thymic stromal lymphopoietin，TSLP）的表达。最终，作者认为，水溶性壳聚糖可以作为治疗过敏性哮喘的新型药物。

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-a, 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-kB 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.