CD68

ABSTRACT Autoantibodies and complement opsonization have been implicated in the process of demyelination in the major human CNS demyelinating disease multiple sclerosis (MS), but scavenger receptors (SRs) may also play pathogenetic roles. We characterized SR mRNA and protein expression in postmortem brain tissue from 13 MS patients in relation to active demyelination. CD68, chemokine (C-X-C motif) ligand 16 (CXCL16), class A macrophage SR (SR-AI/II), LOX-1 (lectin-like oxidized low-density lipoprotein receptor 1), FcγRIII, and LRP-1 (low-density lipoprotein receptor-related protein 1) mRNA were upregulated in the rims of chronic active MS lesions. CD68 and CXCL16 mRNA were also upregulated around chronic active MS lesions. By immunohistochemistry, CD68, CXCL16, and SR-AI/II were expressed by foamy macrophages in the rim and by ramified microglia around chronic active MS lesions. CXCL16 and SR-AI/II were also expressed by astrocytes in MS lesions and by primary human microglia and astrocytes in vitro. These data suggest that SRs are involved in myelin uptake in MS, and that upregulation of CD68, CXCL16, and SR-AI/II is one of the initial events in microglia as they initiate myelin phagocytosis. As demyelination continues, additional upregulation of LOX-1, FcγRIII, and LRP-1 may facilitate this process. >>

ABSTRACT: Exposure of breast tissue to silicone has been associated with autoimmune diseases in the medical literature since the 1960's. Japanese women injected with raw silicone had features of a collagen vascular disease but did not meet criteria for a specific diagnosis. Subsequently, we have seen women with silicone breast implants that have similar problems. We performed a prospective noncontrolled study on women with silicone breast implants. Results from the first 50 consecutive women revealed the most prominent complaints in this group were fatigue (89%), generalized stiffness (75%), poor sleep (71%), and arthralgias (78%). Other problems included Raynaud's phenomenon, alopecia, adenopathy, night sweats, and frequent sore throats. Unexpectedly, half of these women complained of dry eyes and dry mouths. Positive antinuclear antibodies and or rheumatoid factors were discovered in 38% of patients although the anti-SSA antibody was found in only one patient and anti-SSB in none. Labial salivary gland biopsies in 5 cases showed mononuclear cell infiltrates compatible with Sjögren's syndrome in 4. The infiltrating cells were predominantly CD68 positive monocyte/macrophages, which is different from what is found in Sjögren's syndrome. These findings may indicate the presence of a unique syndrome associated with silicone implants that is characterized by musculoskeletal pain and autoimmune features. >>

ABSTRACT: The immunophenotypic characteristics of silicone gel-filled breast and testicular implant capsules have not been well described. Therefore, we studied 17 paraffin-embedded tissue sections from 9 breast implant patients and 1 testicular implant patient to assess the type and extent of inflammatory responses present. Immunohistochemical analyses were performed on paraffin-embedded tissue sections for expression of CD20, CD45RO, betaF1, CD68, CD44, kappa and A immunoglobulin light chains, and bcl-XL (a member of the bcl-2 family of proteins involved in apoptosis). The most common histologic features included prominent T-cell and foamy macrophage reactions with foreign body giant cells and granulomas in a dense fibrovascular connective tissue. Foci of polyclonal plasma cells and acute inflammatory cells were variably present. In one case, there was reactive germinal center formation, a novel finding. A "pseudosynovium" at the implant capsule interface was present in the majority of cases as previously described; it showed reactivity with CD68. Thin strands of highly refractile, nonpolarizable material, consistent with silicone, were regularly noted in intra- and extracellular locations. The immunohistochemical results included reactivity of the majority of lymphocytes with CD45RO and/or betaF1 (confirming an anamnestic reactive T-cell phenotype), and reactivity of the macrophages, giant cells, and "pseudosynovium" with the macrophage/histiocyte marker, CD68. The reactive germinal centers were positive for CD20. Reactivity for CD44, an activation and intracellular adhesion marker, was frequently observed in the foamy macrophages and foreign body giant cells and has not been previously reported. The plasma cells demonstrated polyclonal immunoglobulin light-chain reactivity, consistent with a reactive process. These findings suggest that silicone implants induce chronic inflammatory responses in many adjacent capsules, which consist of anamnestically responding T cells, reactive B-lymphocytes, and macrophages. >>

ABSTRACT: To report pre- and post-operative macular optical coherence tomography (OCT) and immunohistochemical findings in a case of long-lasting silicone oil tamponade followed by silicone oil removal and epimacular membrane peeling. A 69-year-old man with long-standing silicone oil tamponade and an epiretinal membrane at the posterior pole in his right eye (RE) underwent silicone oil/BSS exchange with epiretinal membrane peeling. Preoperatively, RE best-corrected visual acuity was 20/200 and macular OCT examination revealed a small increase in foveal thickness (250 microm) with the appearance of a linear hyper-reflective signal at the foveal vitreoretinal interface and a thicker (440 microm) hyperreflective finding causing posterior shadowing at the vitreoretinal interface inferiorly to the fovea. Histopathologic and immunohistochemical study of the specimen including the epiretinal membrane was performed. Light microscopy revealed extensive rounded empty spaces interpreted as silicone oil bubbles in the preretinal membrane. Macrophages marker (CD68) positive staining cells were found surrounding the empty spaces within the preretinal membrane and several empty spaces were observed intracellularly within macrophage cytoplasm. Thirty days after surgery best-corrected visual acuity was 20/60 and OCT examination showed an evident decrease in foveal thickness (220 microm) with the disappearance of any hyper-reflective signal at the vitreoretinal interface referable to an epiretinal membrane. The immunohistochemical study showed both silicone oil droplets and macrophagic cells embedded in the epiretinal membrane. Postoperative OCT demonstrated retinal recovery after silicone oil removal and epiretinal membrane peeling, thus justifying an unexpected visual acuity recovery despite the very long term tamponade. >>

ABSTRACT: Connective tissue disease-like illness has been associated with silicone breast implants. However, no data are currently available on the immunopathology of the capsule surrounding the breast implants. Sera from women with breast implants were collected and assayed for interleukin-6 (IL-6), IL-2, and hyaluronic acid. Capsular biopsies were stained with a probe for HYA or with monoclonal antibodies specific for human macrophages (CD68), T cells (CD4), IL-6, and IL-2. Control specimens consisted of breast biopsies from women undergoing reduction mammoplasty. Our results revealed an increased local amount of hyaluronic acid in the capsule of patients with breast implants compared with control breast tissue. The HYA was localized extracellularly in areas containing fibrosis and cellular infiltrates. The infiltrating cells were determined to be primarily macrophages and T cells. No IL-6 was localized in any of the tissue sections. In contrast, large amounts of IL-2 were found in regions of infiltrating lymphocytes. No significant increase in IL-6, IL-2, or hyaluronic acid was found in the sera. The role of hyaluronic acid and cytokines in the inflammatory response in the capsules of silicone breast implants is discussed. >>

ABSTRACT: BACKGROUND: Silicone gel-containing breast implants have been widely used for aesthetic and reconstructive mammoplasty. The development of a periprosthetic capsule is considered a local reparative process against the breast implant in which a variety of inflammatory cells may appear. Nevertheless, only few reports have evaluated the immunophenotypes of those inflammatory cells. Herein, we aim to provide more information in this regard evaluating 40 patients with breast implants. METHODS: We studied the immunophenotype of the inflammatory cells of capsular implants using antibodies against lymphocytes (CD3, CD4, CD8, CD20, CD45, and CD30) and histiocytes (CD68). Percentages of CD3 and CD20 positive cells were compared using the unpaired Student's t test. Fisher's test was also used to compare Baker grades by implant type, implant profile, and location and the presence of inflammatory cells by implant type. RESULTS: The associations between Baker grades and implant type and location were statistically nonsignificant (p = 0.42 in both cases). However, the use of low profile implants was significantly associated (p = 0.002) with a higher proportion of Baker grades 3 and 4. We found evidence of inflammation in 92.5 % of all implant capsules, with a statistically significant (p = 0.036) higher proportion in textured breast implants. T cells predominated over B cells. Textured implants elicited a more marked response to T cells than smooth implants, with a similar proportion of helper and cytotoxic T cells. Textured implants showed statistically significant higher percentages of CD3 positive cells than smooth implants. Percentages of CD20 positive cells were similar in textured and smooth implants. CONCLUSIONS: These results suggest that textured breast implants might induce a stronger local T cell immune response. Our findings could shed some light to understand the association of silicone breast implants and some cases of anaplastic large cell lymphomas. Level of Evidence: Level III, prognostic study. >>

ABSTRACT The formation of capsular fibrosis around silicone breast implants is a common complication in reconstructive and plastic surgery. Foreign body reaction-induced infections are quite common because of the hydrophobic surface properties of silicone and are, in addition, considered to be a causative factor of capsular fibrosis.

In this experimental pilot study, 2 groups of 7 Sprague-Dawley rats were established to evaluate the periprosthetic collagen synthesis after implantation of coated silicone implants. In the first group, the textured minisilicone implants were implanted submuscularly. The second group received the biotechnologically, surface-modified phosphorylcholine (PC)-coated implants. After a 3-month period, all the rats were killed, and the capsules were examined in a histologic (hematoxylin-eosin and Masson-trichrom) and immunohistologic way (CD4, CD8, CD68, TGF-beta, fibroblasts, collagen type I, and collagen type III).

Significant differences were found to occur between the PC-coated and standard, textured implants with respect to the inflammatory reaction and collagen synthesis.

The production of hydrophilic surfaces in silicone implants by way of PC-coating causes a decrease in the inflammatory reaction, and thus, a reduction of periprosthetic fibrosis. This could form the basis of a cost-effective, preventive, and therapeutic strategy with respect to the decrease in capsular fibrosis occurrence. >>

ABSTRACT: Connective tissue disease-like illness has been associated with silicone breast implants. However, no data are currently available on the immunopathology of the capsule surrounding the breast implants. Sera from women with breast implants were collected and assayed for interleukin-6 (IL-6), IL-2, and hyaluronic acid. Capsular biopsies were stained with a probe for HYA or with monoclonal antibodies specific for human macrophages (CD68), T cells (CD4), IL-6, and IL-2. Control specimens consisted of breast biopsies from women undergoing reduction mammoplasty. Our results revealed an increased local amount of hyaluronic acid in the capsule of patients with breast implants compared with control breast tissue. The HYA was localized extracellularly in areas containing fibrosis and cellular infiltrates. The infiltrating cells were determined to be primarily macrophages and T cells. No IL-6 was localized in any of the tissue sections. In contrast, large amounts of IL-2 were found in regions of infiltrating lymphocytes. No significant increase in IL-6, IL-2, or hyaluronic acid was found in the sera. The role of hyaluronic acid and cytokines in the inflammatory response in the capsules of silicone breast implants is discussed. >>

ABSTRACT: Silicone-based breast implants continue to be the focus of many studies attempting to correlate implant failure to clinical and pathological factors. Routine pathology of peri-implant capsule is extensively described in the literature. The actual significance of the cellular events remains unconfirmed, particularly with reference to clinical outcome. This study reviews our experience with explanted capsules. The study makes specific reference to the immunohistochemistry of the cells participating in the capsule and the significance of the immunophenotypic characterization of these cells to clinical outcome. The use of a wide selection of immunomarkers for T and B lymphocytes and histiocytes provided no supporting evidence for local cell participation in the capsule, which may indicate the presence of an immunological reaction present in the capsule at the time of explantation. One was only able to confirm the presence of a low grade inflammatory process and progression to fibrosis and calcification over time. Statistical correlation was obtained only between Baker grade of capsular contracture and CD3/CD68 immunomarker positivity. CD45RO did show correlation with pain. No correlation was demonstrated with calcification. The results obtained in this study highlighted the need for further investigations into the mechanism of histiocyte and fibrocyte recruitment and activation in the capsule, a possible source of pain and contracture, which is a serious long-term clinical finding leading to the necessity for explantation. >>

ABSTRACT: To determine the histologic features of granulomatous reactions in persilicone periretinal proliferation. This retrospective study included 12 patients with recurrent retinal detachment and persilicone granulomatous proliferation after vitrectomy for proliferative vitreoretinopathy (PVR). All patients underwent reoperation for membrane surgery. Immunohistochemical study of the excised periretinal membranes was performed with cytokeratins, GFAP, vimentin, CD68, CD45, and lysozyme antibodies. The cellular characteristics of periretinal granulomas allow differentiation of two types of tissue. Spongy tissue (nine cases) showed an accumulation of mature vacuolated macrophages that contained silicone without multinucleated giant cells (MGC). The second type (three cases) consisted of an accumulation of sparsely vacuolated macrophages, epithelioid cells, and MGC. The MGC corresponded to transition forms of foreign body giant cells (FBGC). Spongy tissue was associated with anatomic success (58.3% of cases) and with stabilized PVR (66.7% of cases) at the time of the membrane surgery. MGC were associated with prolonged silicone oil tamponade, recurrent retinal detachment, and progressive PVR. Intraocular silicone oil can lead to periretinal foreign body granulomas. FBGC are occasionally observed and were associated with progressive PVR. >>