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Blood, 15 July 2004, Vol. 104, No. 2, pp. 409-414.
Prepublished online as a Blood First Edition Paper on March 23, 2004; DOI 10.1182/blood-2004-01-0126.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Interleukin-1 but not IL-1 binds to fibrinogen and fibrin and has enhanced activity in the bound form
Abha Sahni,
Min Guo,
Sanjeev K. Sahni, and
Charles W. Francis
From the Hematology/Oncology Unit, Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, NY.
Fibrin is formed at sites of injury or inflammation and provides the temporary matrix to support vascular cell responses that are also mediated by cytokines including interleukin-1 (IL-1). We have shown previously that fibroblast growth factor 2 (FGF-2) binds with high affinity to fibrin(ogen). Because IL-1 has a structure similar to FGF-2, we have investigated the possible binding of IL-1 to fibrin(ogen). Experiments using IL-1 immobilized on Sepharose beads and soluble iodine 125 (125I)-labeled fibrinogen demonstrated no specific interaction of IL-1 with fibrinogen, but IL-1 showed saturable and specific binding. Scatchard analysis indicated a single binding site with an apparent Kd = 1.5 nM and a maximum molar binding ratio of IL-1 to fibrinogen of 1.8:1. Binding of 125I-IL-1 to Sepharose-immobilized fibrinogen also demonstrated a single binding site with an apparent Kd of 3.5 nM. IL-1 also bound specifically to fibrin monomer and polymerized fibrin with apparent Kds of 3.4 nM and 2.3 nM, respectively. IL-1 displaced FGF-2 for binding to fibrin, indicating an interaction with the same or a closely related site. Compared with free form, fibrinogen-bound IL-1 stimulated increased activation of endothelial cell nuclear factor B (NF- B), monocyte chemoattractant protein-1 (MCP-1) secretion, and nitric oxide (NO) synthesis. We conclude that IL-1 binds with high affinity to fibrin(ogen) and demonstrates increased activity in the bound form. (Blood. 2004; 104:409-414)

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