Heparin inhibits ligand binding to the leukocyte integrin Mac-1 (CD11b/CD18).
نویسندگان
چکیده
BACKGROUND 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. METHODS AND RESULTS 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<0.001) to the extent of prolongation of the activated partial thromboplastin time. CONCLUSIONS We describe a pharmacologically relevant property of heparin that may contribute to its benefits in clinical use. The binding of heparin to Mac-1 and the resulting inhibition in binding of Mac-1 ligands may directly modulate coagulation, inflammation, and cell proliferation.
منابع مشابه
Heparin also interacts with selectins and modulates the cell adhesion process.
Modulates the Cell Adhesion Process 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 ...
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ورودعنوان ژورنال:
- Circulation
دوره 100 14 شماره
صفحات -
تاریخ انتشار 1999