title: Expression of Siglec-11 by human and chimpanzee ovarian stromal cells, with uniquely human ligands: implications for human ovarian physiology and pathology.
abstract: 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 of SIGLEC11 transcript 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 of SIGLEC11 into 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.
authors.affiliation: Center for Academic Research and Training in Anthropogeny, Department of Medicine and Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.forename: Renee
authors.initials: R
authors.lastname: Chow
authors.forename: Liwen
authors.initials: L
authors.lastname: Deng
authors.forename: Dan
authors.initials: D
authors.lastname: Anderson
authors.forename: Noel
authors.initials: N
authors.lastname: Weidner
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.forename: Chanda
authors.initials: C
authors.lastname: Bewtra
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.forename: Jack
authors.initials: J
authors.lastname: Bui
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
authors.forename: Nissi
authors.initials: N
authors.lastname: Varki
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D037102:Lectins / Q000096:biosynthesis / Q000235:genetics*; D008024:Ligands; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D010053:Ovary / Q000166:cytology* / Q000276:immunology; D002679:Pan troglodytes; D017154:Stromal Cells / Q000276:immunology*
chemical_list: D037102:Lectins; D008024:Ligands; D008565:Membrane Proteins; C464442:SIGLEC11 protein, human