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Effects of human soluble thrombomodulin on experimental glomerulonephritis
- Source :
- Kidney International. 61(2):490-501
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- Effects of human soluble thrombomodulin on experimental glomerulonephritis. Background Coagulation and inflammation are both important processes that contribute to glomerular injury. The present study was performed to evaluate the effects of recombinant human soluble thrombomodulin (RHS-TM) in a lethal model of thrombotic glomerulonephritis and to investigate the possible mechanisms. Methods Thrombotic glomerulonephritis was induced in rats by administration of lipopolysaccharide and rabbit anti-rat glomerular basement membrane antibody. One hour later, RHS-TM or heparin was administered, and the histological findings, renal functions, and coagulation parameters were evaluated. To evaluate the contribution of carboxypeptidase R (CPR) to the results obtained in rats treated with RHS-TM, plasma CPR levels were measured. Then, carboxypeptidase inhibitor (CPI), which prevents the function of CPR, was administered. Results Massive glomerular thrombosis and lung hemorrhage developed within five hours of disease induction, and all rats died within 24 hours. RHS-TM (3 mg/kg) prevented the progression of the disease and all rats survived. Heparin (250 U/kg/h) showed similar anti-thrombotic effect, but induced massive hemorrhage in the lungs or stomach. RHS-TM attenuated leukocyte/neutrophil infiltration in the glomerulus but heparin did not, suggesting that RHS-TM has anti-inflammatory properties. CPR levels in plasma were about threefold higher in rats treated with RHS-TM compared to those in rats treated with heparin. Furthermore, the inhibitory effect of RHS-TM on leukocyte/neutrophil infiltration was significantly diminished by injection of CPI. Conclusion RHS-TM effectively attenuates the injuries of thrombotic glomerulonephritis in rats. The results indicate that RHS-TM, in addition to its anti-thrombotic action, may exert its anti-inflammatory properties by converting proCPR to CPR, which then inactivates anaphylatoxins. RHS-TM is a potential novel therapeutic tool for thrombotic glomerular injury and related disorders.
- Subjects :
- Anaphylatoxins
Carboxypeptidase B2
kidney
medicine.drug_class
Thrombomodulin
Kidney Glomerulus
Complement C5a
Pharmacology
anaphylatoxin
Blood Urea Nitrogen
Leukocyte Count
Glomerulonephritis
Thrombin
Blood plasma
medicine
Animals
Humans
Lysine Carboxypeptidase
Anaphylatoxin
Rats, Wistar
Blood Coagulation
Fibrin
Kidney
Platelet Count
business.industry
Anticoagulant
anticoagulant
Thrombosis
Heparin
medicine.disease
glomerular injury
thrombin
Rats
carboxypeptidase
Disease Models, Animal
medicine.anatomical_structure
Solubility
inflammation
Nephrology
Creatinine
Immunology
Prothrombin Time
Female
Partial Thromboplastin Time
Rabbits
business
medicine.drug
Subjects
Details
- ISSN :
- 00852538
- Volume :
- 61
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Kidney International
- Accession number :
- edsair.doi.dedup.....8a2df25917d436375d762b0075c8d067
- Full Text :
- https://doi.org/10.1046/j.1523-1755.2002.00160.x