0
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Adhesion Molecule Expression in Postischemic Microvascular Dysfunction: Activity of a Micronized Purified Flavonoid Fraction

      ,

      Journal of Vascular Research

      S. Karger AG

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Ischemia and reperfusion (I/R) induces neutrophil infiltration in skeletal muscle that is localized to the ischemic region. To transmigrate at ischemic regions, granulocytes must first arrest in the postcapillary venular segment of the microcirculation. Initially, leukocytes roll along the endothelium of these venules, a weak adhesive interaction that is mediated by the selectins (L-, E-, and P-selectin). Leukocyte rolling functions to slow the neutrophil during its transit through the microcirculation, thereby allowing it to monitor its local environment for the presence of activating factors arising from the ischemic tissues. When activated, the rolling granulocyte is rendered capable of forming the stronger adhesive interactions that allow the cell to become arrested in postcapillary venules in the ischemic region. These adhesive interactions are mediated by a leukocyte glycoprotein complex designated CD11/CD18 and intercellular adhesion molecule-1 (ICAM-1) expressed on endothelial cells. The stationary neutrophil uses the gradient in concentration of soluble chemoattractants liberated from ischemic tissues as a directional cue to move from the vascular to extravascular compartment, being guided in its transit across the endothelium by interactions with platelet endothelial cell adhesion molecule-1 (PECAM-1), an adhesive molecule localized to the interendothelial cleft. This paper reviews current understanding of the mechanisms underlying the establishment of leukocyte/endothelial cell interactions in postischemic skeletal muscle in terms of specific adhesion molecules that participate in neutrophil sequestration after I/R. Discovery of the molecular determinants of neutrophil/endothelial cell adhesion has uncovered potential mechanisms whereby agents exhibiting anti-adhesive properties may act. The micronized purified flavonoid fraction (450 mg diosmin, 50 mg hesperidin) prevents I/R-induced leukocyte adhesion in skeletal muscle. This anti-adhesive effect appears to be mediated at least in part by inhibition of induced expression of ICAM-1.

          Related collections

          Most cited references 4

          • Record: found
          • Abstract: found
          • Article: not found

          Endothelial cell interactions with granulocytes: tethering and signaling molecules.

          The adhesion of granulocytes to endothelial cells requires regulated expression of molecules on both the endothelial cell and the granulocyte. These pro-adhesive molecules have diverse structures and mechanisms of expression, and act either to tether the two cells together or as signals that induce activation-dependent adhesion events. Combinations of tethering and signaling molecules regulate endothelial-cell-granulocyte interactions at the endothelial surface.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The neutrophil selectin LECAM-1 presents carbohydrate ligands to the vascular selectins ELAM-1 and GMP-140.

            LECAM-1 (leukocyte-endothelial cell adhesion molecule 1), the lymphocyte lectin ("selectin") homing receptor for peripheral lymph nodes (PLNs), participates in the earliest interactions of polymorphonuclear neutrophilic leukocytes (PMNs) with inflamed venules. Here, we present evidence that LECAM-1 mediates this function through a novel mechanism--presentation of oligosaccharide ligands to the inducible vascular selectins endothelial-leukocyte adhesion molecule (ELAM-1) and granule membrane protein 140 (GMP-140). PMN, but not lymphocyte, LECAM-1 is modified with the vascular selectin ligand sialyl Lewis x (sLex) and specifically binds ELAM-1-transfected cells. Although only a small fraction of total cell surface sLex, LECAM-1-associated sLex appears to play a prominent role in PMN interactions with cell-associated ELAM-1 and GMP-140, as anti-LECAM-1 monoclonal antibodies or selective removal of cell surface LECAM-1 inhibits PMN binding to vascular selectin transfectants by up to 70%. The enhanced function of LECAM-1-associated sLex may reflect the striking concentration, shown here, of LECAM-1 on PMN surface microvilli, the site of initial cellular contact.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              H2O2 and tumor necrosis factor-alpha activate intercellular adhesion molecule 1 (ICAM-1) gene transcription through distinct cis-regulatory elements within the ICAM-1 promoter.

              We investigated the mechanisms by which H2O2 increases intercellular adhesion molecule 1 (ICAM-1; CD54) expression in endothelial cells. The H2O2-induced increase in ICAM-1 mRNA was inhibited by actinomycin D, by the antioxidant N-acetylcysteine, and by 3-amino-benzamide (which blocks oxidant-induced AP-1 activity), but not by pyrrolidine dithiocarbamate (which blocks oxidant-induced NF-kappa B activity). Nuclear run-on and transient transfections of ICAM-1 promoter constructs indicated that H2O2 stimulated ICAM-1 gene transcription by activation of a distinct region of the ICAM-1 promoter. The H2O2-responsive element was localized to sequences between -981 and -769 (relative to start codon). Located within this region are two 16-base pair repeats, each containing binding sites for the transcription factors AP-1 and Ets. A similar composite AP-1/Ets element isolated from the macrophage scavenger receptor gene conferred H2O2 responsiveness to a minimal promoter. Mutation of the 16-base pair repeats within the ICAM-1 promoter prevented H2O2-induced DNA binding activity, and their deletion abrogated the H2O2-induced transcriptional activity. In contrast, TNF alpha induced ICAM-1 transcription via activation of promoter sequences between -393 and -176, a region with C/EBP and NF-kappa B binding sites. The results indicate that H2O2 activates ICAM-1 transcription through AP-1/Ets elements within the ICAM-1 promoter, which are distinct from NF-kappa B-mediated ICAM-1 expression induced by TNF alpha.
                Bookmark

                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                978-3-8055-6933-0
                978-3-318-00479-3
                1018-1172
                1423-0135
                1999
                August 1999
                27 August 1999
                : 36
                : Suppl 1
                : 15-23
                Affiliations
                Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, School of Medicine in Shreveport, Shreveport, La., USA
                Article
                54070 J Vasc Res 1999;36(suppl 1):15–23
                10.1159/000054070
                10474047
                © 1999 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: 3, References: 31, Pages: 9
                Categories
                Paper

                General medicine, Neurology, Cardiovascular Medicine, Internal medicine, Nephrology

                Comments

                Comment on this article