RESUMO
OBJECTIVES: Pigmented cells, that contain inert, submicron-sized dietary particles, are a consistent feature of the base of human Peyer's patches (PP). We aimed (i) to phenotype these intestinal pigment cells (PC) in archival tissue specimens and (ii) to establish whether PC phenotype is altered in inflammatory conditions, especially Crohn's disease (CD). METHODS: PCs contained within PP were identified by routine haematoxylin and eosin (H&E) staining and dark field microscopy of archival ileal sections for: adenocarcinoma (n=16), colonic CD (n=23), non-CD colitis (n=10). Paraffin-embedded serial sections were graded for microscopic inflammation and then investigated immunohistochemically with antibodies against CD68, MAC387, CD14, CD11b, CD15, CD1a, S100, HLA-DR, CD86 and Cathepsin D. Analyses were by light and confocal microscopies. RESULTS: The majority of PCs were CD68 positive (circa 80%) with a minority (circa 20%) staining for MAC387. Microparticles were mainly identified within cathepsin D negative lysosomal compartments. Histological inflammatory grade and disease type had no influence on cell phenotype. CONCLUSIONS: The microparticle-containing PCs of the PP base are mainly mature macrophages (CD68) of low metabolic and immunological activity. There is no evidence of differential PC phenotype or activation in differing disease states, including CD.
Assuntos
Íleo/patologia , Corpos de Inclusão/metabolismo , Inflamação/patologia , Nódulos Linfáticos Agregados , Fenótipo , Pigmentação , Antígenos CD/metabolismo , Catepsina D/metabolismo , Doença de Crohn/patologia , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Nódulos Linfáticos Agregados/citologia , Nódulos Linfáticos Agregados/patologiaRESUMO
OBJECTIVES: The aims of this study were to determine, in peripheral blood mononuclear cells (PBMC), whether particulate antigen triggers (i) an amplified cell proliferative response compared to soluble antigen and (ii) a dysfunctional response in cells derived from patients with chronic inflammation and specifically in those with inflammatory bowel disease (IBD). SUBJECTS: Healthy volunteers (n = 17), inflammatory controls (n = 8) and patients with IBD (n = 17) were recruited from St Thomas' and Guys' Hospital, London, UK. METHODS: Following optimisation of experimental conditions (0.1-10.0 mug/ml antigen), PBMC were stimulated with (i) 10.0 mug/ml recombinant soluble heat shock protein 65 (hsp 65) and (ii) 1.0 and 10.0 mug/ml hsp 65 conjugated to microparticles (0.5 mum diameter). PBMC proliferative responses were measured by (3)H-Thymidine incorporation at day 5 and results compared between groups using unpaired t-test. RESULTS: Conjugation to microparticles of low dose hsp 65 significantly increased overall proliferative responses by 2-11 fold compared to soluble antigen alone (p < 0.05). However, no specific PBMC proliferative dysregulation was noted in cells from subjects with IBD. CONCLUSIONS: Low dose antigen, in microparticulate form, leads to amplified cell proliferation in primary human cells, as showed previously in cell lines and animal studies. However there is no abnormal proliferative response in cells from subjects with IBD.
Assuntos
Proliferação de Células , Proteínas de Choque Térmico/imunologia , Doenças Inflamatórias Intestinais/imunologia , Leucócitos Mononucleares/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Fatores de TempoRESUMO
We have studied the relationship between metal ion levels and lymphocyte counts in patients with metal-on-metal hip resurfacings. Peripheral blood samples were analysed for lymphocyte subtypes and whole blood cobalt and chromium ion levels in 68 patients (34 with metal-on-metal hip resurfacings and 34 with standard metal-on-polyethylene total hip replacements). All hip components were radiologically well-fixed and the patients were asymptomatic. Cobalt and chromium levels were significantly elevated in the patients with metal-on-metal hip resurfacings, compared with the patients with standard metal-on-polyethylene designs (p < 0.0001). There was a statistically significant decrease in the level of CD8(+) cells (T-cytotoxic/suppressor) (p = 0.005) in the metal-on-metal hip resurfacing group. A threshold level of blood cobalt and chromium ions was associated with reduced CD8(+) T-cell counts. We have no evidence that our patients suffered as a result of this reduced level of CD8(+) T-cells.