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

Abha Sahni, Min Guo, Sanjeev Sahni, Charles W. Francis

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)409-414
Number of pages6
JournalBlood
Volume104
Issue number2
DOIs
StatePublished - Jul 15 2004
Externally publishedYes

Fingerprint

Fibrin
Interleukin-1
Fibrinogen
Fibroblast Growth Factor 2
Sepharose
Binding Sites
Endothelial cells
Iodine
Blood Vessels
Monocytes
Nitric Oxide
Endothelial Cells
Chemical activation
Cytokines
Inflammation

ASJC Scopus subject areas

  • Hematology

Cite this

Interleukin-1β but not IL-1α binds to fibrinogen and fibrin and has enhanced activity in the bound form. / Sahni, Abha; Guo, Min; Sahni, Sanjeev; Francis, Charles W.

In: Blood, Vol. 104, No. 2, 15.07.2004, p. 409-414.

Research output: Contribution to journalArticle

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abstract = "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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AB - 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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