CL-L1 and CL-K1 Exhibit Widespread Tissue Distribution With High and Co-Localized Expression in Secretory Epithelia and Mucosa
CL-L1 and CL-K1 Exhibit Widespread Tissue Distribution With High and Co-Localized Expression in Secretory Epithelia and Mucosa
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DOI：
10.3389/fimmu.2018.01757
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发表时间：
2018-07-31
影响因子：
7.3
通讯作者：
Henriksen, Maiken L.
中科院分区：
文献类型：
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作者：
Hansen, Soren W. K.;Aagaard, Josephine B.;Henriksen, Maiken L.
肝集合素 1（CL-L1，别名集合素 10）和肾集合素 1（CL-K1，别名集合素 11）是与补体系统相关的寡聚模式识别分子，其中任何一个基因的突变都可能导致缺陷和发育缺陷。据报道，这两种集合素在肝脏、肾脏和肾上腺中定位和合成，并且可以在循环中以异聚复合物 (CL-LK) 的形式存在，该复合物与微生物高甘露糖样糖缀合物结合后，通过凝集素激活途径激活补体系统。同种异体的组织分布异聚 CL-L1 和 -K1 复合物、异聚复合物形成的机制以及这种情况发生在哪些组织中，迄今尚未完全描述。我们通过使用单克隆抗体的免疫组织化学方法解决了两种集合素在主要人体组织中的精确细胞定位问题。我们发现这两种集合素具有广泛且几乎相同的组织分布，在内/外分泌组织和粘膜的上皮细胞中高表达。 mRNA 转录物的定位和蛋白质的检测之间也存在一致性，表明局部合成可能负责外周定位和 CL-LK 复合物的最终形成。内/外分泌分泌组织和粘膜中高表达的功能意义尚不清楚，但可能与 MASP-3 的活性有关，MASP-3 具有相似的表达模式，并且已知可增强替代补体激活途径的活性。
Collectin liver 1 (CL-L1, alias collectin 10) and collectin kidney 1 (CL-K1, alias collectin 11) are oligomeric pattern recognition molecules associated with the complement system, and mutations in either of their genes may lead to deficiency and developmental defects. The two collectins are reportedly localized and synthesized in the liver, kidneys, and adrenals, and can be found in the circulation as heteromeric complexes (CL-LK), which upon binding to microbial high mannose-like glycoconjugates activates the complement system via the lectin activation pathway. The tissue distribution of homo-vs. heteromeric CL-L1 and -K1 complexes, the mechanism of heteromeric complex formation and in which tissues this occurs, is hitherto incompletely described. We have by immunohistochemistry using monoclonal antibodies addressed the precise cellular localization of the two collectins in the main human tissues. We find that the two collectins have widespread and almost identical tissue distribution with a high expression in epithelial cells in endo-/exocrine secretory tissues and mucosa. There is also accordance between localization of mRNA transcripts and detection of proteins, showing that local synthesis likely is responsible for peripheral localization and eventual formation of the CL-LK complexes. The functional implications of the high expression in endo-/exocrine secretory tissue and mucosa is unknown but might be associated with the activity of MASP-3, which has a similar pattern of expression and is known to potentiate the activity of the alternative complement activation pathway.