Regulated on activation, normal T-cell-expressed and -secreted mRNA expression in normal endometrium and endometriotic implants: assessment of autocrine/paracrine regulation by in situ hybridization.
Chemoattraction of macrophages and T cells into the normal endometrium and inflammatory sites within endometriotic foci is mediated by chemokine gene expression. mRNA transcripts encoding regulated on activation, normal T-cell-expressed and -secreted (RANTES), a monocyte and T-cell chemokine, were demonstrated in the stroma of normal endometrium and endometriotic implants using in situ mRNA hybridization. Epithelial glands failed to express RANTES mRNA. In histological serial sections, we observed CD68-positive macrophages in the stroma of endometriotic implants adjacent to regions with prominent RANTES mRNA hybridization. In adjacent sections, monoclonal antibodies against tumor necrosis factor (TNF)-alpha showed this cytokine to be localized to stromal and epithelial compartments of the endometriotic implant with weak staining in unaffected ovarian tissue. Subconfluent monolayers of endometriotic stromal cells were tested for RANTES gene expression in situ, but we could only detect RANTES mRNA in isolated stromal cells after treatment with TNF-alpha. No RANTES mRNA was observed in unstimulated stromal cells or TNF-alpha stimulated or unstimulated epithelial cells. The data are consistent with a model in which proinflammatory cytokines (eg, TNF-alpha) induce RANTES gene expression limited to specific cells within endometrial and endometriotic stroma. Production of this chemokine, in turn, stimulates recruitment of CD68-positive macrophages into these tissues.
Hornung
D
D
Departments of Obstetrics and Gynecology and Molecular Pathology, University of Tuebingen, Tuebingen, Germany.
Klingel
K
K
Dohrn
K
K
Kandolf
R
R
Wallwiener
D
D
Taylor
R N
RN
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D019898:Autocrine Communication; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000737:chemistry; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000096:biosynthesis; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018946:Chemokine CCL5; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule