Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Endothelium is a target tissue for tumor necrosis factor

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6999933
; ; ; ;
Tumor necrosis factor/cachectin (TNF) is a mediator of the septic state, which involves diffuse abnormalities of coagulation throughout the vasculature. Since previous studies have demonstrated that endothelial cells can play an active role in coagulation, they examined if TNF could modulate endothelial cell hemostatic properties. Incubation of purified recombinant TNF with cultured endothelial cells resulted in time and dose-dependent acquisition of tissue factor procoagulant activity. Concomitant with enhanced procoagulant activity, TNF also suppressed endothelial cell cofactor activity for the anticoagulant protein C pathway; both thrombin-mediated protein C activation and formation of functional activated protein C-protein S complex on the cell surface were considerably attenuated. Thus, TNF induced a unidirectional shift in cell surface hemostatic properties favoring promotion of clot formation. This led us to carry out binding studies with /sup 125/I-TNF. TNF bound to monolayers in a saturable manner with half-maximal binding at 120pM. Interaction of TNF with the endothelium led to synthesis and elaboration of interleukin-1 (IL-1). IL-1 generation was half-maximal at a TNF concentration of approx. 150pM. These data indicate that IL-1 can bind to endothelium resulting in modulation of its hemostatic properties and elaboration of IL-1. Endothelium can thus play an integral role in the host response to neoplastic and inflammatory stimuli.
Research Organization:
Oklahoma Medical Research Foundation, Oklahoma City
OSTI ID:
6999933
Report Number(s):
CONF-8604222-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
Country of Publication:
United States
Language:
English

Similar Records

Human recombinant interleukin-1 beta- and tumor necrosis factor alpha-mediated suppression of heparin-like compounds on cultured porcine aortic endothelial cells
Journal Article · Sat Sep 01 00:00:00 EDT 1990 · Journal of Cellular Physiology; (USA) · OSTI ID:6511681
Monocyte chemoattractant protein-1 but not tumor necrosis factor-alpha is correlated with monocyte infiltration in mouse lipid lesions
Journal Article · Sun Jan 10 23:00:00 EST 1999 · Circulation · OSTI ID:842487
Activation of endothelial-leukocyte adhesion molecule 1 (ELAM-1) gene transcription
Journal Article · Thu Aug 01 00:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States) · OSTI ID:5822746

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BLOOD COAGULATION FACTORS
BODY
COAGULANTS
DAYS LIVING RADIOISOTOPES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
GROWTH FACTORS
HEMATOLOGIC AGENTS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LYMPHOKINES
MITOGENS
NECROSIS
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
SYNTHESIS
TIME DEPENDENCE
TISSUES
TRACER TECHNIQUES