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      Comparative CD43 Behavior on Monocytes and Lymphocytes in Kidney Transplants

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          Abstract

          In human cultured monocytic cells stimulated by cytokines, CD43 was demonstrated to exhibit a modification of sialylated epitopes (dys-sialylation) [Soler et al: Leukoc Biol 1997;61:609–618]. Therefore, we chose to investigate CD43 behavior on patients who present pathological status implicating monocytes after renal graft (KTR). We performed flow cytometry after immune staining using monoclonal antibodies to CD43 sialic acid-dependent (L60) and -independent (L10) epitopes. Compared to normal controls, mean fluorescence intensity was never altered on lymphocytes. Conversely, on monocytes, we found different profiles with L60: 26% of patients having normal CD43 expression, 54% displayed decreased values and 20% had a double population of monocytes, the major one being normal and the minor one with a very low staining. Decreased values were more frequent among KTR during the first 3 months following transplantation. L10 immunostaining was not altered on monocytes in patients with low values of CD43 staining by L60, confirming that the mechanism involved was a CD43 dys-sialylation. We investigated a possible role of cyclosporin (CsA) on human monocytic (THP-1) and lymphoid (Jurkat) cell lines. CsA decreases CD43 expression in monocytic and not in lymphoid cell lines and could be responsible for the specific dys-sialylation of KTR monocytes. Whatever, CD43 dys-sialylation might lead to functional abnormalities of monocytes in KTR, possibly involving the adhesion process.

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          Most cited references 3

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          Negative regulation of T-cell adhesion and activation by CD43.

          CD43 is a cell-surface sialoglycoprotein expressed by a variety of haematopoietically derived cells, including T lymphocytes. Earlier observations of defective CD43 expression by T lymphocytes from boys with the X-chromosome-linked Wiskott-Aldrich syndrome suggested the importance of CD43 in lymphocyte function. Subsequent studies have suggested that CD43 facilitates leukocyte adhesion and has a co-stimulatory role during T-cell activation. To define the physiologically relevant function(s) of CD43, we have generated CD43-knockout mice. We report here that CD43-deficient T cells from such mice show a marked increase in their in vitro proliferative response to concanavalin A, anti-CD3, the superantigen SEB and allostimulation. Additionally, CD43-deficient T cells show a substantial enhancement in homotypic adhesion and in their ability to bind different ligands, including fibronectin and the intercellular adhesion molecule ICAM-1. Vaccinia-virus-infected CD43-knockout mice mounted an augmented anti-vaccinia cytotoxic T-cell response compared with their wild-type littermates, yet developed an increased virus load. We conclude that CD43 negatively regulates T-cell activation and adhesion and is important for viral clearance.
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            Identification of two subpopulations of rat monocytes expressing disparate molecular forms and quantities of CD43.

            Expression of CD43 (leukosialin, sialophorin) by rat blood monocytes was analyzed by flow cytometric, microscopic, and biochemical techniques. Monocytes were identified cytometrically using a combination of light-scatter parameters and binding of the anti-monocyte/macrophage monoclonal antibody (mAb) OX-41. Two-color flow cytometry studies with W3/13 and HIS 17, two anti-CD43 mAb that react with different antigenic epitopes, revealed two subpopulations of monocytes expressing disparate levels of CD43 (referred to hereafter as hi-CD43 MO and lo-CD43 MO). In three-color flow cytometry studies, hi-CD43 MO were found to express higher levels of CD4 than lo-CD43 MO; in contrast, lo-CD43 MO bound higher levels of RP-3, a mAb raised against rat neutrophils. Hi- and lo-CD43 MO expressed comparable amounts of CD14, CD45, and intercellular adhesion molecule-1 (CD54); hi-CD43 MO expressed somewhat more lymphocyte function-associated antigen-1 alpha chain (CD11a) and CD18 than their lo-CD43 MO counterparts. A minority of cells in both subpopulations expressed class II histocompatibility antigens. Hi- and lo-CD43 MO isolated by fluorescence-activated cell sorting had features typical of monocytes as assessed by light and electron microscopy. In Western blotting experiments, lo-CD43 MO and elicited peritoneal macrophages were found to express a less heavily sialylated form of CD43 than hi-CD43 MO.
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              Enhancement of T-cell activation by the CD43 molecule whose expression is defective in Wiskott-Aldrich syndrome.

              CD43 (sialophorin, leukosialin, leukocyte large sialoglycoprotein), a heavily sialylated molecule found on most leukocytes and platelets, was initially identified as a major glycoprotein of mouse, rat and human T cells. CD43 expression is defective on the T cells of males with the Wiskott-Aldrich syndrome, an X chromosome-linked recessive immunodeficiency disorder. Affected males are susceptible to opportunistic infections and do not respond to polysaccharide antigens, reflecting defects in cytotoxic and helper T-cell functions. Anti-CD43 monoclonal antibodies have a modest costimulatory effect on T cells, natural killer cells, B cells and monocytes, and one such antibody has been shown to activate T cells directly. To investigate a possible physiological role for CD43, a complementary DNA encoding the human protein was introduced into an antigen-responsive murine T-cell hybridoma. We observed that CD43 enhances the antigen-specific activation of T cells and that the intracellular domain of CD43, which is hyperphosphorylated during T-cell activation, is required for this function. We also found that antigen-presenting cells can bind specifically to immobilized purified CD43 and that the binding can be inhibited by liposomes containing CD43 as well as by anti-CD43 monoclonal antibodies.
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                Author and article information

                Journal
                NEF
                Nephron
                10.1159/issn.1660-8151
                Nephron
                S. Karger AG
                1660-8151
                2235-3186
                2000
                November 2000
                08 November 2000
                : 86
                : 3
                : 292-297
                Affiliations
                aINSERM U 387, bService de Néphrologie et cService d’Anesthésie et de Réanimation, Hôpital de Sainte-Marguerite, Marseille, France
                Article
                45784 Nephron 2000;86:292–297
                10.1159/000045784
                11096286
                © 2000 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, References: 24, Pages: 6
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/45784
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                Kidney transplants, Lymphocytes, CD43, Cyclosporin, Monocytes

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