title: Interleukin-1beta but not IL-1alpha 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 ((125)I)-labeled fibrinogen demonstrated no specific interaction of IL-1alpha with fibrinogen, but IL-1beta 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-1beta to fibrinogen of 1.8:1. Binding of (125)I-IL-1beta to Sepharose-immobilized fibrinogen also demonstrated a single binding site with an apparent K(d) of 3.5 nM. IL-1beta also bound specifically to fibrin monomer and polymerized fibrin with apparent K(d)s of 3.4 nM and 2.3 nM, respectively. IL-1beta 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-1beta stimulated increased activation of endothelial cell nuclear factor kappaB (NF-kappaB), monocyte chemoattractant protein-1 (MCP-1) secretion, and nitric oxide (NO) synthesis. We conclude that IL-1beta binds with high affinity to fibrin(ogen) and demonstrates increased activity in the bound form.
authors.affiliation: Department of Medicine, PO Box 610, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA. abha_sahni@urmc.rochester.edu
authors.forename: Abha
authors.initials: A
authors.lastname: Sahni
authors.forename: Min
authors.initials: M
authors.lastname: Guo
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Sahni
authors.forename: Charles W
authors.initials: CW
authors.lastname: Francis
mesh_terms: D001667:Binding, Competitive / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D009569:Nitric Oxide / Q000378:metabolism; D012685:Sepharose; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D018932:Chemokine CCL2; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D016222:Fibroblast Growth Factor 2; D009569:Nitric Oxide; D005337:Fibrin; D005340:Fibrinogen; D012685:Sepharose