Interleukin-1β but not IL-1α binds to fibrinogen and fibrin and has enhanced activity in the bound form

Abstract

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-1α with fibrinogen, but IL-1β showed saturable and specific binding. Scatchard analysis indicated a single binding site with an apparent K_d = 1.5 nM and a maximum molar binding ratio of IL-1β to fibrinogen of 1.8:1. Binding of ¹²⁵I-IL-1β to Sepharose-immobilized fibrinogen also demonstrated a single binding site with an apparent K_d of 3.5 nM. IL-1β also bound specifically to fibrin monomer and polymerized fibrin with apparent K_ds 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 chemoattractant protein-1 (MCP-1) secretion, and nitric oxide (NO) synthesis. We conclude that IL-1β binds with high affinity to fibrin(ogen) and demonstrates increased activity in the bound form. (Blood. 2004; 104:409-414)