title: Fibroblast heterogeneity: existence of functionally distinct Thy 1(+) and Thy 1(-) human female reproductive tract fibroblasts.
abstract: Little is known about fibroblasts from the female reproductive tract, much less whether or not functional subsets exist. Fibroblasts are key as sentinel cells for recruiting white blood cells and for wound healing. The purpose of this research was to evaluate the possibility that functional subsets of fibroblasts exist in the human female reproductive tract. The strategy used was to define fibroblast subpopulations based on their surface expression of the Thy 1 antigen. In situ staining of human myometrium and endometrium showed heterogeneous staining for Thy 1. Freshly derived strains of fibroblasts from the myometrium and endometrium also demonstrated heterogeneous Thy 1 expression. For the first time, using magnetic beading and fluorescence-activated cell sorting, human myometrial fibroblasts were successfully separated into functionally unique Thy 1(+) and Thy 1(-) subsets. Both subsets produced the proinflammatory cytokines interleukin (IL)-6 and IL-8 after IL-1beta stimulation, but only the Thy 1(+) subset produced MCP-1. Furthermore, only Thy 1(+) fibroblasts up-regulated CD40 surface expression with IL-1beta or interferon-gamma treatment. Engagement of CD40 in the Thy 1(+) subpopulation induced IL-6, IL-8, and MCP-1. The discovery of functional subsets of reproductive tract fibroblasts now permits assessment of their roles in the normal functions of the reproductive tract and in disease states such as adhesions and menorrhagia.
authors.affiliation: Department of Microbiology and Immunology, Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
authors.forename: L
authors.initials: L
authors.lastname: Koumas
authors.forename: A E
authors.initials: AE
authors.lastname: King
authors.forename: H O
authors.initials: HO
authors.lastname: Critchley
authors.forename: R W
authors.initials: RW
authors.lastname: Kelly
authors.forename: R P
authors.initials: RP
authors.lastname: Phipps
mesh_terms: D019013:CD40 Antigens / Q000378:metabolism / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004717:Endometrium / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D014644:Genetic Variation; D005836:Genitalia, Female / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D009215:Myometrium / Q000166:cytology / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D019013:CD40 Antigens; D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D018800:Thy-1 Antigens; D023201:CD40 Ligand