This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yanaka, K. Articles by Kübler, W. Search for Related Content PubMed PubMed Citation Articles by Yanaka, K. Articles by Kübler, W. Related Collections Heparin Brain Circulation and Metabolism Anticoagulants

(Circulation. 2000;102:e169.)
© 2000 American Heart Association, Inc.

Correspondence

Heparin Also Interacts With Selectins and Modulates the Cell Adhesion Process

Kiyoyuki Yanaka, MD, PhD

Noriyuki Kato, MD

Tadao Nose, MD, PhD

Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan, kyanaka@md.tsukuba.ac.jp

To the Editor:

We read with great interest the article by Peter and coworkers¹ in the October 5, 1999 issue of Circulation in which the authors demonstrated the binding of heparin to integrin Mac-1 on stimulated leukocytes. Recent investigations have revealed that heparin can modulate biological processes, such as binding to adhesion receptors on endothelial cells and leukocytes.² Leukocyte adhesion is a complex molecular process, and multiple adhesion receptor systems mediate the recruitment of leukocytes from the blood. The initial trafficking of circulating leukocytes to sites of inflammation is mediated by the selectin family of adhesion receptors; this is followed by the engagement of additional cellular recognition receptors, including the immunoglobulin superfamily and integrins. Heparin interacts with adhesion molecules, including integrin Mac-1 (CD11b/CD18) and selectins.^{3 4}

Peter and colleagues speculated that the binding of heparin to Mac-1 and the consequent inhibition of Mac-1 ligand binding could directly modulate coagulation, inflammation, and cell proliferation. They failed to mention the role of other adhesion molecules, such as selectins, in this process. We would like to bring to the authors’ attention our study on the role of heparin in the cell adhesion process.⁵ This study revealed that heparin inhibits leukocyte adhesion by antagonizing the function of selectins. We evaluated the efficacy of sulfated polysaccharides (unfractionated heparin, low-molecular-weight heparin, heparan sulfate, chondroitin sulfate, and dextran sulfate) on leukocyte accumulation in the infarcted brain and found that the administration of these sulfated polysaccharides led to reduced leukocyte accumulation. The relative potency of leukocyte accumulation inhibition of . . . [Full Text of this Article]

Karlheinz Peter, MD

Meike Schwarz, MD

Thomas Nordt, MD

Christoph Bode, MD

Department of Internal Medicine III, University of Freiburg, Hugstetter Str 55, 79106 Freiburg, Germany, peter@med1.ukl.uni-freiburg.de

Christian Conradt, PhD

Martin Moser, MD

Wolfgang Kübler, MD

Departments of Internal Medicine III and Biometry, University of Heidelberg, Germany