Interleukin-1beta but not IL-1alpha binds to fibrinogen and fibrin and has enhanced activity in the bound form.
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.
Sahni
Abha
A
Department of Medicine, PO Box 610, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA. abha_sahni@urmc.rochester.edu
Guo
Min
M
Sahni
Sanjeev K
SK
Francis
Charles W
CW
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
D018932:Chemokine CCL2; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D016222:Fibroblast Growth Factor 2; D009569:Nitric Oxide; D005337:Fibrin; D005340:Fibrinogen; D012685:Sepharose