Hyaluronan deposition and co-localization with inflammatory cells and collagen in a murine model of fungal allergic asthma.
Hyaluronan deposition and co-localization with inflammatory cells and collagen in a murine model of fungal allergic asthma.
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DOI：
10.1007/s00011-014-0719-3
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发表时间：
2014-06
影响因子：
6.7
通讯作者：
Schuh, Jane M.
中科院分区：
文献类型：
--
作者：
Ghosh, Sumit;Samarasinghe, Amali E.;Hoselton, Scott A.;Dorsam, Glenn P.;Schuh, Jane M.
过敏性哮喘是一种气道慢性炎症性疾病，其特征是过度炎症和气道壁细胞外基质（ECM）及相关细胞的重塑。在炎症条件下，ECM的主要成分透明质酸（HA）发生动态变化，这可能反过来影响炎症细胞的募集和激活，导致过敏性哮喘的急慢性免疫病理。在本研究中，我们在烟曲霉小鼠过敏性哮喘吸入模型中测量了炎症部位产生的HA水平的变化，并研究了其对炎症反应和胶原沉积的影响。我们发现过敏动物的血凝素水平升高，并且这种升高与第二次过敏原攻击后5天炎症细胞的涌入有关。这种HA水平的增加主要是由于透明质酸酶-1 （HYAL1）和透明质酸酶-2 （HYAL2）的上调。此外，透明质酸与新胶原合成和沉积区域共定位。总的来说，我们的发现有助于越来越多的文献关注ECM成分作为炎症介质，而不仅仅是结构支持产品。真菌性过敏性哮喘中HA定位的证据为在小鼠模型中更密切地研究HA与过敏性白细胞的关系提供了动力。进一步研究透明质酸在介导细胞反应中的作用可能有助于开发治疗因真菌致敏引起的严重哮喘患者的靶点。
Allergic asthma is a chronic inflammatory disease of the airways characterized by excessive inflammation and remodeling of the extracellular matrix (ECM) and associated cells of the airway wall. Under inflammatory conditions, hyaluronan (HA), a major component of the ECM, undergoes dynamic changes, which may in turn affect the recruitment and activation of inflammatory cells leading to acute and chronic immunopathology of allergic asthma. In the present study, we measured the changes in HA levels generated at sites of inflammation and examined its effect on inflammatory responses and collagen deposition in an Aspergillus fumigatus murine inhalational model of allergic asthma. We found that HA levels are elevated in allergic animals and that the increase correlated with the influx of inflammatory cells 5 days after the second allergen challenge. This increase in HA levels appeared largely due to up regulation of hyaluronidase-1 (HYAL1) and hyaluronidase-2 (HYAL2). Furthermore, HA co-localizes with areas of new collagen synthesis and deposition. Overall our findings contribute to the growing literature that focuses on the components of ECM as inflammatory mediators rather than mere structural support products. The evidence of HA localization in fungal allergic asthma provides the impetus to study HA more closely with allergic leukocytes in murine models. Further studies examining HA’s role in mediating cellular responses may help to develop targets for treatment in patients with severe asthma due to fungal sensitization.
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影响因子：
33.6
作者：
Jiang D;Liang J;Noble PW
通讯作者：
Noble PW
影响因子：
2.9
作者：
Hoselton, Scott A.;Samarasinghe, Amali E.;Schuh, Jane M.
通讯作者：
Schuh, Jane M.
DOI：
10.1016/0020-711x(92)90040-8
发表时间：
1992-03-01
期刊：
INTERNATIONAL JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
DEUDON, E;BERROU, E;PICARD, J
通讯作者：
PICARD, J
影响因子：
0.7
作者：
Necas, J.;Bartosikova, L.;Kolar, J.
通讯作者：
Kolar, J.
影响因子：
6.9
作者：
Cheng, Georgiana;Swaidani, Shadi;Sharma, Manisha;Lauer, Mark E.;Hascall, Vincent C.;Aronica, Mark A.
通讯作者：
Aronica, Mark A.