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Expression of Siglec-11 by Human and Chimpanzee Ovarian Stromal Cells, with Uniquely Human Ligands: Implications for Human Ovarian Physiology and Pathology. Wang X et al. Siglecs 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. We earlier 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 et al. Science 309: 1693). Analyzing human gene microarrays to define new patterns of expression, we observed high levels of SIGLEC11 transcript in ovary and adrenal cortex. Thus, we examined human and chimpanzee tissues using a well-characterized anti-Siglec-11 mouse monoclonal antibody. While 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 of SIGLEC11 into a primary human ovarian stromal fibroblast cell line altered secretion of GRO-alpha, IL-10, IL-7, TGF-beta1, and TNF-alpha, 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 to 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.
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