Expression of Siglec-11 by human and chimpanzee ovarian stromal cells, with uniquely human ligands: implications for human ovarian physiology and pathology.
Expression of Siglec-11 by human and chimpanzee ovarian stromal cells, with uniquely human ligands: implications for human ovarian physiology and pathology.
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人类和黑猩猩卵巢基质细胞表达 Siglec-11，具有独特的人类配体：对人类卵巢生理学和病理学的影响。
DOI：
10.1093/glycob/cwr039
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发表时间：
2011
期刊：
影响因子：
4.3
通讯作者：
Varki,Nissi
中科院分区：
文献类型：
--
作者：
Wang,Xiaoxia;Chow,Renee;Deng,Liwen;Anderson,Dan;Weidner,Noel;Godwin,AndrewK;Bewtra,Chanda;Zlotnik,Albert;Bui,Jack;Varki,Ajit;Varki,Nissi
Siglecs（唾液酸结合免疫球蛋白超家族凝集素）是i型凝集素组的细胞表面信号受体，可识别唾液酸承载聚糖。cd33相关siglecs是一个主要在造血细胞中表达的亚群，其功能与免疫反应相关。早前我们报道了一个人类特异性基因转换事件，该事件显著改变了siglece -11细胞外结构域的编码区，与人类在小胶质细胞中的特异性表达有关（Hayakawa T, Angata T, Lewis AL, Mikkelsen TS, Varki NM, Varki a . 2005）。小胶质细胞中的人类特异性基因。科学。309:1693)。通过分析人类基因微阵列来定义新的表达模式，我们在卵巢和肾上腺皮质中观察到高水平的siglec11转录本。因此，我们使用一种特性良好的抗siglece -11小鼠单克隆抗体检测了人类和黑猩猩组织。尽管肾上腺的表达是可变的，并且仅限于毛细血管中的巨噬细胞浸润，但人类和黑猩猩卵巢中Siglec-11的表达都在成纤维细胞上，这是Siglec在间充质来源的基质细胞上表达的第一个例子。来自卵巢间质成纤维细胞的细胞因子在卵泡发育和排卵中起重要作用。siglec11稳定转染人卵巢原代间质成纤维细胞系改变了生长调节癌基因α、白细胞介素(IL)-10、IL-7、转化生长因子β1和肿瘤坏死因子-α等参与卵巢生理的细胞因子的分泌。对siglece -11配体的探测显示，与黑猩猩卵巢中的弥漫性基质配体相比，人类卵巢中的肥大细胞表达明显而强烈。有趣的是，与绝经前相比，绝经后卵巢中siglece -11的表达有增加的趋势。在人类卵巢间质瘤和人类特异性疾病多囊卵巢综合征中也发现了siglece -11的表达。这些结果提示siglece -11在卵巢生理和人类进化中的潜在作用。
Siglecs (Sialic acid-binding Immunoglobulin Superfamily Lectins) are cell surface signaling receptors of the I-type lectin group that recognize sialic acid-bearing glycans. CD33-related-Siglecs are a subset with expression primarily in cells of hematopoietic origin and functional relevance to immune reactions. Earlier we reported a human-specific gene conversion event that markedly changed the coding region for the extracellular domain of Siglec-11, associated with human-specific expression in microglia (Hayakawa T, Angata T, Lewis AL, Mikkelsen TS, Varki NM, Varki A. 2005. A human-specific gene in microglia.Science. 309:1693). Analyzing human gene microarrays to define new patterns of expression, we observed high levels ofSIGLEC11transcript in the ovary and adrenal cortex. Thus, we examined human and chimpanzee tissues using a well-characterized anti-Siglec-11 mouse monoclonal antibody. Although adrenal expression was variable and confined to infiltrating macrophages in capillaries, ovarian expression of Siglec-11 in both humans and chimpanzees was on fibroblasts, the first example of Siglec expression on mesenchyme-derived stromal cells. Cytokines from such ovarian stromal fibroblasts play important roles in follicle development and ovulation. Stable transfection ofSIGLEC11into a primary human ovarian stromal fibroblast cell line altered the secretion of growth-regulated oncogene α, interleukin (IL)-10, IL-7, transforming growth factor β1 and tumor necrosis factor-α, cytokines involved in ovarian physiology. Probing for Siglec-11 ligands revealed distinct and strong mast cell expression in human ovaries, contrasting to diffuse stromal ligands in chimpanzee ovaries. Interestingly, there was a trend of increased Siglec-11 expression in post-menopausal ovaries compared with pre-menopausal ones. Siglec-11 expression was also found on human ovarian stromal tumors and in polycystic ovarian syndrome, a human-specific disease. These results indicate potential roles for Siglec-11 in ovarian physiology and human evolution.