title: Cellular and molecular composition of fibrous capsules formed around silicone breast implants with special focus on local immune reactions.
abstract: During the past 30 years, much debate has centered around side effects of silicone breast implants. Meta-analyses rejected the presumed relationship between silicone breast implants and connective tissues diseases but, in seeming contradiction, case reports about connective tissue diseases and rheumatoid symptoms continue to be published. We analyzed the cellular and molecular composition of fibrous capsules removed from patients at various times after surgery for diagnostic purposes (breast cancer relapse) or to relieve painful constrictive fibrosis. Frozen sections of capsule tissue were immunohistochemically stained for subsets of lymphocytes, macrophages, dendritic cells, fibroblasts, smooth muscle cells, for collagenous and non-collagenous extracellular matrix proteins, for heat shock protein 60 (HSP60) and for adhesion molecules. Massive deposition of fibronectin and tenascin was observed adjacent to the implant surface. The capsule/silicone implant contact zone was consistently characterized by a palisade-like single or multilayered cell accumulation consisting of HSP60+ macrophages and HSP60+ fibroblasts. Mononuclear cell infiltrates consisting of activated CD4+ T-cells, expressing CD25 and CD45RO, as well as macrophages were detected beneath the contact zone as well as perivascularly. Importantly, many Langerhans-cell like dendritic cells (DCs) were found with a predilection at the frontier layer zone abutting the silicone implant. Also, at this site, massive expression of ICAM-1, but not VCAM-1 or ELAM-1 emerged. Endothelial cells of the intracapsular neovasculature were P-Selectin+. Our results show that silicone induces a strong local T-cell immune response and future studies will determine the specificity and function of these T-lymphocytes.
authors.affiliation: Institute of Pathophysiology, University Innsbruck, Medical School, Fritz-Pregl-Strasse 3, 6020 Innsbruck, Austria.
authors.forename: Dolores
authors.initials: D
authors.lastname: Wolfram
authors.forename: Wolfram
authors.initials: W
authors.lastname: Dolores
authors.forename: Christian
authors.initials: C
authors.lastname: Rainer
authors.forename: Rainer
authors.initials: R
authors.lastname: Christian
authors.forename: Harald
authors.initials: H
authors.lastname: Niederegger
authors.forename: Niederegger
authors.initials: N
authors.lastname: Harald
authors.forename: Hildegunde
authors.initials: H
authors.lastname: Piza
authors.forename: Piza
authors.initials: P
authors.lastname: Hildegunde
authors.forename: Georg
authors.initials: G
authors.lastname: Wick
authors.forename: Wick
authors.initials: W
authors.lastname: Georg
mesh_terms: D000328:Adult; D018427:Breast Implants; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D018834:Chaperonin 60 / Q000276:immunology / Q000378:metabolism; D003094:Collagen / Q000276:immunology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007109:Immunity; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D018613:Microscopy, Confocal; D008875:Middle Aged; D020034:Silicone Gels
chemical_list: D015815:Cell Adhesion Molecules; D018834:Chaperonin 60; D016326:Extracellular Matrix Proteins; D020034:Silicone Gels; D003094:Collagen