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Protein C inhibits endocytosis of thrombin-thrombomodulin complexes in A549 lung cancer cells and human umbilical vein endothelial cells

Journal Article · · Blood; (United States)
OSTI ID:6280178
;

We investigated the effect of protein C on the endocytosis of thrombin-thrombomodulin complexes. We previously showed that exposure of umbilical vein endothelial cells to thrombin stimulated the internalization and degradation of thrombin. A similar internalization was stimulated by a monoclonal antithrombomodulin antibody. We have repeated these studies in the presence of protein C and found that endocytosis of /sup 125/I-thrombin-thrombomodulin complexes, but not /sup 125/I-antithrombomodulin-thrombomodulin complexes, is inhibited. Activated protein C did not inhibit endocytosis of thrombin-thrombomodulin complexes. Protein C inhibited both internalization and degradation of /sup 125/I-thrombin and diisopropylphosphoryl (DIP) /sup 125/I-thrombin in human lung cancer cells (A549). These effects were observed at protein C concentrations found in human plasma. Protein S had no effect on the inhibition of endocytosis of thrombin-thrombomodulin complexes by protein C. We propose that protein C may regulate the rate of endocytosis of thrombin-thrombomodulin complexes in vivo and thereby control the capacity for endothelium to activate protein C.

Research Organization:
Washington Univ. School of Medicine, St Louis, MO
OSTI ID:
6280178
Journal Information:
Blood; (United States), Journal Name: Blood; (United States) Vol. 5; ISSN BLOOA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CHEMICAL REACTIONS
COAGULANTS
COMPLEXES
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DIGESTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
ENZYMES
FETAL MEMBRANES
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
INTERMEDIATE MASS NUCLEI
INTRACELLULAR DIGESTION
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LUNGS
MAMMALS
MAN
MEMBRANES
MONOCLONAL ANTIBODIES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HYDROLASES
PRIMATES
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RESPIRATORY SYSTEM
SERINE PROTEINASES
THROMBIN
TISSUES
TRACER TECHNIQUES
TUMOR CELLS
VERTEBRATES