ABSTRACT
The presence of cytokines in the peripheral nerve was positively correlated to the induction and progression of inflammation during experimental allergic neuritis (EAN) and Guillain Barré syndrome (GBS). We investigated the induction of adhesion molecules such as L-selectin, E-selectin, ICAM-1, VCAM-1 and Mac-1 on Schwann cells by proinflammatory cytokines. Cultured human Schwann cells from normal adult, fetal and diabetic nerves were studied by immunofluorescence at basal condition and after stimulation with cytokines for 6, 24, 48 and 96 h. Incubation of human Schwann cells with TNFalpha, IFNgamma and IL-1beta induces the expression of ICAM-1 starting at 6 h and reaching a peak at 24 h on more than 90% of cells. VCAM-1 expression was induced after 6 h of treatment with TNFalpha and IL-1beta on almost 100% of Schwann cells. Surprisingly, stimulation with TNFalpha, IFNgamma and IL-1beta also induced the expression of L-selectin on fetal and diabetic Schwann cells, but not on normal adult cells. E-selectin, an adhesion molecule classically upregulated during inflammation, as well as Mac-1, a ligand for ICAM-1, were not expressed on human Schwann cells at basal condition or after treatment with cytokines. No ICAM-1, VCAM-1 and L-selectin expression was found on unstimulated Schwann cells. Our results suggest that upregulation of adhesion molecules on Schwann cells may have a role in the pathogenesis of inflammation in the peripheral nerve.
Subject(s)
Cell Adhesion Molecules/drug effects , Cytokines/pharmacology , Inflammation Mediators/pharmacology , Schwann Cells/drug effects , Adult , Cell Adhesion Molecules/biosynthesis , Cells, Cultured , Diabetes Mellitus , E-Selectin/biosynthesis , E-Selectin/drug effects , Fetus , Fluorescent Antibody Technique , Humans , Intercellular Adhesion Molecule-1/biosynthesis , Intercellular Adhesion Molecule-1/drug effects , Interferon-gamma/pharmacology , Interleukin-1/pharmacology , Interleukin-8/pharmacology , L-Selectin/biosynthesis , L-Selectin/drug effects , Macrophage-1 Antigen/biosynthesis , Macrophage-1 Antigen/drug effects , Schwann Cells/metabolism , Time Factors , Tumor Necrosis Factor-alpha/pharmacology , Vascular Cell Adhesion Molecule-1/biosynthesis , Vascular Cell Adhesion Molecule-1/drug effectsABSTRACT
Non-classical antigen-presentation by CD1 molecules expressed on cytokine-activated monocytes (CAM), and cell-mediated responses supported by double-negative (DN) and by CD8+ responder alphabeta T cells, are involved in host resistance against mycobacterial infections. The CD1b protein is responsible for presentation of non-peptide, lipid antigens to T cells. In this context, a pivotal role is played by induction of CD1b protein on the membrane of human monocytes activated by GM-CSF alone, and more efficiently by GM-CSF combined with IL-4. Rifampin (RFP), a drug which is extensively utilized for chemoprophylaxis or treatment of Mycobacterium tuberculosis, is known to reduce a number of B, or T cell-dependent responses. Therefore we undertook immunopharmacological studies on RFP, to determine the effects of this agent on human macrophage function, relative to antigen presentation by CD1b molecules and on DN T cell cytolytic function. The results showed that: (a) graded concentration of RFP (2 or 10 microg/ml) induced a significant increase of CD1b expression, in CAM as evaluated by FACS analysis; (b) RFP increased significantly the specific mAb binding to CD1b on CAM surface; (c) treatment of effector cells with RFP did not reduce DN T cell-mediated cytolysis against lymphoblastoid cells transfected with CD1b cDNA (C1R.b6 cells), pulsed with M. tuberculosis. These results suggest that RFP could be of potential value in improving mycobacterial antigen presentation without impairing responder T cell function.
Subject(s)
Antibiotics, Antitubercular/pharmacology , Antigens, Bacterial/immunology , Antigens, CD1/biosynthesis , Glycolipids/immunology , Mycobacterium tuberculosis/immunology , Rifampin/pharmacology , T-Lymphocytes/immunology , Cell Adhesion , Cell Line , Cell Membrane/immunology , Cytotoxicity, Immunologic , Flow Cytometry , Fluorescent Antibody Technique, Direct , Humans , Indicators and Reagents , Monocytes/immunology , Mycobacterium tuberculosis/drug effects , T-Lymphocytes/drug effectsABSTRACT
Strong immunogenicity is induced by antitumor triazene compounds in tumor cells through a mutagenic mechanism. A highly immunogenic <