Heparin inhibits ligand binding to the leukocyte integrin Mac-1 (CD11b/CD18)

The clinical benefits of heparin reach beyond its anticoagulative properties. Recently, it has been described that leukocytes adhere on immobilized heparin mediated by the integrin Mac-1 (CD11b/CD18, alphaMbeta2, or CR3). Because inhibition of this versatile adhesion molecule could explain various a...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 1999-10, Vol.100 (14), p.1533-1539
Main Authors: PETER, K, SCHWARZ, M, CONRADT, C, NORDT, T, MOSER, M, KÜBLER, W, BODE, C
Format: Article
Language:English
Subjects:
Animals
Anticoagulants - pharmacology
Biological and medical sciences
Blood. Blood coagulation. Reticuloendothelial system
Factor X - metabolism
Fibrinogen - metabolism
Granulocytes - metabolism
Heparin - metabolism
Heparin - pharmacology
Humans
Intercellular Adhesion Molecule-1 - metabolism
Macrophage-1 Antigen - metabolism
Medical sciences
Mice
Monocytes - metabolism
Partial Thromboplastin Time
Pharmacology. Drug treatments
Tetradecanoylphorbol Acetate - pharmacology
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Summary:The clinical benefits of heparin reach beyond its anticoagulative properties. Recently, it has been described that leukocytes adhere on immobilized heparin mediated by the integrin Mac-1 (CD11b/CD18, alphaMbeta2, or CR3). Because inhibition of this versatile adhesion molecule could explain various aspects of the beneficial clinical effects of heparin, we evaluated whether soluble heparin modulates Mac-1 function in vitro and in vivo. Binding of unfractionated heparin to Mac-1 on PMA-stimulated monocytes and granulocytes was directly demonstrated in flow cytometry, whereas no binding of heparin was detected on unstimulated leukocytes. Unfractionated heparin inhibited binding of the soluble ligands fibrinogen, factor X, and iC3b to Mac-1. Adhesion of the monocytic cell line THP-1 and of peripheral monocytes and granulocytes to immobilized ICAM-1 was impaired by unfractionated heparin, to the same extent as with inhibition of Mac-1 by monoclonal antibodies such as c7E3. Low-molecular-weight heparin also inhibits binding of fibrinogen to Mac-1. Additionally, flow cytometry of whole blood preparations of patients treated with unfractionated heparin revealed an inhibitory effect of heparin on the binding of fibrinogen to Mac-1 that correlates (n= 48, r=0.63, P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.cir.100.14.1533