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Thrombin and factor Xa enhance neutrophil chemoattractant production after ischemia/reperfusion in the rat liver. 2000

Y Yamaguchi, and K Okabe, and J Liang, and H Ohshiro, and K Ishihara, and S Uchino, and J L Zhang, and H Hidaka, and S Yamada, and M Ogawa
Department of Surgery II, Kumamoto University Medical School, Kumamoto, Japan.

BACKGROUND Clotting proteases may affect leukocyte effector function. Activation of the coagulation cascade after ischemia/reperfusion stimulates cytokine production by activated macrophages. Cytokine-induced neutrophil chemoattractant (CINC) may also be important in the pathophysiology of liver ischemia/reperfusion injury. We investigated the effects of a selective factor Xa inhibitor, DX-9065a, on CINC expression after ischemia/reperfusion in the rat liver. METHODS Liver ischemia was induced in rats by occluding the portal vein for 30 min. DX-9065a (9 mg/kg) was injected intravenously 5 min before vascular clamping. Serum CINC concentrations were measured by enzyme-linked immunosorbent assay. Levels of CINC mRNA in the liver were determined by Northern blot analysis. We also examined in vitro CINC production by peritoneal macrophages in response to alpha-thrombin or factor Xa. RESULTS Serum CINC concentrations increased and peaked 6 h after reperfusion. However, pretreatment of animals with DX-9065a resulted in significantly smaller increases in CINC after reperfusion. Pretreatment with DX-9065a also significantly reduced CINC mRNA levels in the liver after ischemia/reperfusion. In vitro CINC production by peritoneal macrophages was enhanced by alpha-thrombin, as well as factor Xa. CONCLUSIONS Thrombin and factor Xa stimulate CINC production by macrophages. A selective inhibitor of factor Xa, DX-9065a, attenuates neutrophil chemoattractant production after ischemia/reperfusion injury of the rat liver.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007728 Kupffer Cells Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood and dispose of worn out red blood cells. Kupffer Cell,Cell, Kupffer,Cells, Kupffer
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D009281 Naphthalenes Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D011422 Propionates Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure. Propanoate,Propanoic Acid,Propionate,Propanoates,Propanoic Acid Derivatives,Propanoic Acids,Propionic Acid Derivatives,Propionic Acids,Acid, Propanoic,Acids, Propanoic,Acids, Propionic,Derivatives, Propanoic Acid,Derivatives, Propionic Acid
D002630 Chemotactic Factors Chemical substances that attract or repel cells. The concept denotes especially those factors released as a result of tissue injury, microbial invasion, or immunologic activity, that attract LEUKOCYTES; MACROPHAGES; or other cells to the site of infection or insult. Chemoattractant,Chemotactic Factor,Chemotaxin,Chemotaxins,Cytotaxinogens,Cytotaxins,Macrophage Chemotactic Factor,Chemoattractants,Chemotactic Factors, Macrophage,Macrophage Chemotactic Factors,Chemotactic Factor, Macrophage,Factor, Chemotactic,Factor, Macrophage Chemotactic
D006133 Growth Substances Signal molecules that are involved in the control of cell growth and differentiation. Mitogens, Endogenous,Endogenous Mitogens
D006490 Hemostatics Agents acting to arrest the flow of blood. Absorbable hemostatics arrest bleeding either by the formation of an artificial clot or by providing a mechanical matrix that facilitates clotting when applied directly to the bleeding surface. These agents function more at the capillary level and are not effective at stemming arterial or venous bleeding under any significant intravascular pressure. Antihemorrhagic,Hemostatic,Antihemorrhagics

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