Hyaluronan Rafts on Airway Epithelial Cells
Hyaluronan Rafts on Airway Epithelial Cells
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DOI：
10.1074/jbc.m115.704288
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发表时间：
2016-01-15
影响因子：
4.8
通讯作者：
Hascall, Vincent
中科院分区：
文献类型：
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作者：
Abbadi, Amina;Lauer, Mark;Hascall, Vincent
许多细胞，包括小鼠气道上皮细胞，通过合成保持附着在细胞表面的白细胞粘附透明质酸（HA）电缆来响应各种炎症刺激。这项研究表明，在没有炎症刺激的情况下，小鼠气道上皮细胞 (AEC) 的气液界面培养物也会主动合成并释放大部分 HA 到纤毛顶端表面，形成重链透明质酸 (HC-HA) 基质。这些基质与绳状 HA 电缆不同，而是以不同的片状或筏状形式存在，可以捕获并嵌入细胞悬浮液中的白细胞。 HC-HA 修饰涉及从α间抑制剂 (I α I) 蛋白聚糖转移重链，该蛋白聚糖的硫酸软骨素链上有两条重链（HC1 和 HC2）。 HC 从硫酸软骨素到 HA 的酯交换转移是由肿瘤坏死因子诱导基因 6 (TSG-6) 介导的，该基因在炎症反应中上调。因为 AEC 培养物没有 TSG-6，也没有血清（I α I 的来源），所以进行了 HC 和 TSG-6 的测定。结果表明，AEC 合成 TSG-6 及其自身重链供体（pre-I α I）和单个重链 3 (HC3)，这些重链也由人肾近端肾小管上皮细胞组成型表达。这些白细胞粘附 HC3-HA 结构也在幼鼠的支气管肺泡灌洗液中发现，并在其顶端纤毛表面观察到。因此，这些白细胞粘附的HA筏现在被鉴定为HC3-HA复合物，它可能是宿主防御机制的一部分，填补了我们目前对小鼠气道上皮生物学和分泌物的理解中的一些重要空白。
Many cells, including murine airway epithelial cells, respond to a variety of inflammatory stimuli by synthesizing leukocyteadhesive hyaluronan (HA) cables that remain attached to their cell surfaces. This study shows that air-liquid interface cultures of murine airway epithelial cells (AECs) also actively synthesize and release a majority of their HA onto their ciliated apical surfaces to form a heavy chain hyaluronan (HC-HA) matrix in the absence of inflammatory stimuli. These matrices do not resemble the rope-like HA cables but occur in distinct sheets or rafts that can capture and embed leukocytes from cell suspensions. The HC-HA modification involves the transfer of heavy chains from the inter-alpha-inhibitor (I alpha I) proteoglycan, which has two heavy chains (HC1 and HC2) on its chondroitin sulfate chain. The transesterification transfer of HCs from chondroitin sulfate to HA is mediated by tumor necrosis factor-induced gene 6 (TSG-6), which is up-regulated in inflammatory reactions. Because the AEC cultures do not have TSG-6 nor serum, the source of I alpha I, assays for HCs and TSG-6 were done. The results show that AECs synthesize TSG-6 and their own heavy chain donor (pre-I alpha I) with a single heavy chain 3 (HC3), which are also constitutively expressed by human renal proximal tubular epithelial cells. These leukocyte adhesive HC3-HA structures were also found in the bronchoalveolar lavage of naive mice and were observed on their apical ciliated surfaces. Thus, these leukocyte-adhesive HA rafts are now identified as HC3-HA complexes that could be part of a host defense mechanism filling some important gaps in our current understanding of murine airway epithelial biology and secretions.