Fibrin is formed at sites of injury of 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 (1251I)-labeled fibrinogen demonstrated no specific interaction of IL-1α with fibrinogen, but IL-1β 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-1β p to fibrinogen of 1.8:1. Binding of 125I-IL-1β to Sepharose-immobilized fibrinogen also demonstrated a single binding site with an apparent Kd of 3.5 nM. IL-1β also bound specifically to fibrin monomer and polymerized fibrin with apparent Kds of 3.4 nM and 2.3 nM, respectively. IL-1β 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-1β stimulated increased activation of endothelial cell nuclear factor κB (NF-κB), monocyte chemoottractant protein-1 (MCP-1) secretion, and nitric oxide (NO) synthesis. We conclude that IL-β binds with high affinity to fibrin(ogen) and demonstrates increased activity in the bound form.
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