FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation
FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation
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DOI：
10.1152/ajplung.00429.2017
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发表时间：
2018-08-01
影响因子：
4.9
通讯作者：
Sriramarao, P.
中科院分区：
文献类型：
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作者：
Ge, Xiao Na;Bastan, Idil;Sriramarao, P.
脂肪酸结合蛋白4（FABP 4）是脂质结合蛋白家族的一员，已知其通过调节细胞内事件如脂质通量和信号传导的能力在炎症中发挥作用。研究表明FABP 4在过敏性哮喘中的促炎作用，尽管其在嗜酸性粒细胞（募集到过敏性气道的主要炎性细胞）中的表达和功能尚未研究。我们研究了FABP 4在小鼠嗜酸性粒细胞中的表达及其在体外调节细胞募集以及在蟑螂抗原（CRA）诱导的过敏性气道炎症中的作用。CRA暴露导致野生型（WT）小鼠中表达FABP 4的炎性细胞（特别是嗜酸性粒细胞）的气道募集。嗜酸性粒细胞中的FABP 4表达由TNF-α以及IL-4和IL-13诱导。与WT细胞相比，FABP 4缺陷型嗜酸性粒细胞在血管细胞粘附分子-1上的细胞铺展/前缘形成显著减少，与细胞间粘附分子-1的粘附显著减少，并伴有β 2-整联蛋白表达减少。此外，FABP 4缺陷的嗜酸性粒细胞表现出减少的迁移，F-肌动蛋白聚合，钙流量，和ERK（1/2）磷酸化响应嗜酸性粒细胞趋化因子-1。在体内，与WT小鼠相比，CRA激发的FABP 4缺陷小鼠表现出减弱的嗜酸性粒细胞增多症和显著降低的气道炎症（气道反应性改善，IL-5、IL-13、TNF-α和半胱氨酰白三烯C4水平降低，气道结构变化减少）。总之，FABP 4在嗜酸性粒细胞中的表达是在炎症条件下诱导的，并且通过促进嗜酸性粒细胞粘附和迁移以及促进气道炎症的各个方面的发展而在过敏性哮喘的发展中起促炎作用。
Fatty acid binding protein 4 (FABP4), a member of a family of lipid-binding proteins, is known to play a role in inflammation by virtue of its ability to regulate intracellular events such as lipid fluxes and signaling. Studies have indicated a proinflammatory role for FABP4 in allergic asthma although its expression and function in eosinophils, the predominant inflammatory cells recruited to allergic airways, were not investigated. We examined expression of FABP4 in murine eosinophils and its role in regulating cell recruitment in vitro as well as in cockroach antigen (CRA)-induced allergic airway inflammation. CRA exposure led to airway recruitment of FABP4-expressing inflammatory cells, specifically eosinophils, in wild-type (WT) mice. FABP4 expression in eosinophils was induced by TNF-alpha as well as IL-4 and IL-13. FABP4-deficient eosinophils exhibited markedly decreased cell spreading/formation of leading edges on vascular cell adhesion molecule-1 and significantly decreased adhesion to intercellular adhesion molecule-1 associated with reduced beta 2-integrin expression relative to WT cells. Furthermore, FABP4-deficient eosinophils exhibited decreased migration, F-actin polymerization, calcium flux, and ERK(1/2) phosphorylation in response to eotaxin-1. In vivo, CRA-challenged FABP4-deficient mice exhibited attenuated eosinophilia and significantly reduced airway inflammation (improved airway reactivity, lower IL-5, IL-13, TNF-alpha, and cysteinyl leukotriene C4 levels, decreased airway structural changes) compared with WT mice. In conclusion, expression of FABP4 in eosinophils is induced during conditions of inflammation and plays a proinflammatory role in the development of allergic asthma by promoting eosinophil adhesion and migration and contributing to the development of various aspects of airway inflammation.