PMID- 15039285
OWN - NLM
STAT- MEDLINE
DCOM- 20040817
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 104
IP  - 2
DP  - 2004 Jul 15
TI  - Interleukin-1beta but not IL-1alpha binds to fibrinogen and fibrin and has 
      enhanced activity in the bound form.
PG  - 409-14
AB  - 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.
FAU - Sahni, Abha
AU  - Sahni A
AD  - Department of Medicine, PO Box 610, University of Rochester Medical Center, 601 
      Elmwood Ave, Rochester, NY 14642, USA. abha_sahni@urmc.rochester.edu
FAU - Guo, Min
AU  - Guo M
FAU - Sahni, Sanjeev K
AU  - Sahni SK
FAU - Francis, Charles W
AU  - Francis CW
LA  - eng
GR  - HL-30616/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040323
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (Iodine Radioisotopes)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9001-31-4 (Fibrin)
RN  - 9001-32-5 (Fibrinogen)
RN  - 9012-36-6 (Sepharose)
SB  - IM
MH  - Binding, Competitive/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Endothelium, Vascular/cytology
MH  - Fibrin/*metabolism
MH  - Fibrinogen/*metabolism
MH  - Fibroblast Growth Factor 2/metabolism
MH  - Humans
MH  - Interleukin-1/*metabolism/pharmacology
MH  - Iodine Radioisotopes
MH  - Nitric Oxide/metabolism
MH  - Sepharose
MH  - Umbilical Veins/cytology
EDAT- 2004/03/25 05:00
MHDA- 2004/08/18 05:00
CRDT- 2004/03/25 05:00
PHST- 2004/03/25 05:00 [pubmed]
PHST- 2004/08/18 05:00 [medline]
PHST- 2004/03/25 05:00 [entrez]
AID - S0006-4971(20)55135-5 [pii]
AID - 10.1182/blood-2004-01-0126 [doi]
PST - ppublish
SO  - Blood. 2004 Jul 15;104(2):409-14. doi: 10.1182/blood-2004-01-0126. Epub 2004 Mar 
      23.