title: Immunohistochemical analysis of sarcoid granulomas. Evaluation of Ki67+ and interleukin-1+ cells.
abstract: Proliferating cells have been immunophenotypically characterized in lymph node and bronchoalveolar lavage (BAL) samples obtained from patients with active and inactive sarcoidosis with the cell-cycle-related antigen Ki67. Ki67 monoclonal antibody was used by combined immunohistochemical methods together with antibodies recognizing macrophage- and T-cell-subset-related antigens using avidin-biotin peroxidase (ABC) and alkaline phosphatase-anti-alkaline phosphatase (APAAP) systems. Many proliferating Ki67+ cells were found in affected mediastinal lymph nodes. These cells were mainly located around granulomas and exhibited phenotypical markers of helper/inducer T cells (CD3+, CD4+). Ki67+ macrophages could not be detected in the same lesions with this technique. A different picture was found in BAL preparations where proportions of both T lymphocytes and macrophages were Ki67+. The presence of replicating lymphocytes could be correlated to disease activity, whereas the proportions of Ki67+ macrophages did not show significant differences between active and inactive disease. Interleukin-1 (IL-1) expression was investigated in the same samples with a specific antiserum. Epithelioid macrophages in granulomas and BAL macrophages in all cases exhibited cytoplasmic staining revealing an activated status. Interestingly, giant cells in granulomas were mainly devoid of IL-1 immunoreactivity. These studies support the concept that activated cells at different sites of ongoing inflammation play a central role in the mechanisms accounting for granuloma formation.
authors.affiliation: Istituto di Anatomia Patologica, University of Verona, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Chilosi
authors.forename: F
authors.initials: F
authors.lastname: Menestrina
authors.forename: P
authors.initials: P
authors.lastname: Capelli
authors.forename: L
authors.initials: L
authors.lastname: Montagna
authors.forename: M
authors.initials: M
authors.lastname: Lestani
authors.forename: G
authors.initials: G
authors.lastname: Pizzolo
authors.forename: A
authors.initials: A
authors.lastname: Cipriani
authors.forename: C
authors.initials: C
authors.lastname: Agostini
authors.forename: L
authors.initials: L
authors.lastname: Trentin
authors.forename: R
authors.initials: R
authors.lastname: Zambello
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis* / Q000276:immunology; D001980:Bronchi / Q000473:pathology; D005260:Female; D006099:Granuloma / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007375:Interleukin-1 / Q000032:analysis*; D019394:Ki-67 Antigen; D008198:Lymph Nodes / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D012507:Sarcoidosis / Q000276:immunology / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007375:Interleukin-1; D019394:Ki-67 Antigen