|
|
Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-08-2406.
 Previous Article | Table of Contents | Next Article 
Blood, 15 April 2003, Vol. 101, No. 8, pp. 3029-3036
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Antithrombin reduces ischemia/reperfusion-induced renal injury in
rats by inhibiting leukocyte activation through promotion of
prostacyclin production
Akio Mizutani,
Kenji Okajima,
Mitsuhiro Uchiba,
Hirotaka Isobe,
Naoaki Harada,
Sachiko Mizutani, and
Takayuki Noguchi
From the Intensive Care Unit, Oita Medical University,
Japan; Department of Laboratory Medicine, Kumamoto
University School of Medicine, Japan; Department of
Pharmacology, Fukuoka University School of Medicine,
Japan; and Department of Maternal-Pediatric Nursing, Oita
Medical University, Japan.
Antithrombin (AT) supplementation in patients with severe sepsis
has been shown to improve organ failures in which activated leukocytes
are critically involved. However, the precise mechanism(s) for the
therapeutic effects of AT is not well understood. We examined in rats
whether AT reduces ischemia/reperfusion (I/R)-induced renal injury by
inhibiting leukocyte activation. AT markedly reduced the I/R-induced
renal dysfunction and histologic changes, whereas neither dansyl
glutamylglycylarginyl chloromethyl ketone-treated factor Xa
(DEGR-F.Xa), a selective inhibitor of thrombin generation, nor
Trp49-modified AT, which lacks affinity for heparin, had any effect.
Renal tissue levels of 6-keto-PGF1 , a stable metabolite of prostacyclin (PGI2), increased after renal I/R. AT
enhanced the I/R-induced increases in renal tissue levels of
6-keto-PGF1, whereas neither DEGR-F.Xa nor
Trp49-modified AT had any effect. AT significantly inhibited
I/R-induced decrease in renal tissue blood flow and the increase
in the vascular permeability. Ischemia/reperfusion-induced increases in renal tissue levels of tumor necrosis factor- ,
cytokine-induced neutrophil chemoattractant, and myeloperoxidase were
significantly inhibited in animals given AT. Pretreatment of animals
with indomethacin reversed the effects induced by AT. Iloprost, an
analog of PGI2, produced effects similar to those induced
by AT. These observations strongly suggest that AT reduces the
I/R-induced renal injury by inhibiting leukocyte activation. The
therapeutic effects of AT might be mainly mediated by PGI2
released from endothelial cells through interaction of AT with cell
surface glycosaminoglycans.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Chappell, M. Jacob, K. Hofmann-Kiefer, M. Rehm, U. Welsch, P. Conzen, and B. F. Becker
Antithrombin reduces shedding of the endothelial glycocalyx following ischaemia/reperfusion
Cardiovasc Res,
July 15, 2009;
83(2):
388 - 396.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Nitescu, E. Grimberg, S.-E. Ricksten, N. Marcussen, and G. Guron
Thrombin inhibition with melagatran does not attenuate renal ischaemia-reperfusion injury in rats
Nephrol. Dial. Transplant.,
August 1, 2007;
22(8):
2149 - 2155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Tsuboi, Y. Naito, K. Katada, T. Takagi, O. Handa, S. Kokura, H. Ichikawa, N. Yoshida, M. Tsukada, and T. Yoshikawa
Role of the thrombin/protease-activated receptor 1 pathway in intestinal ischemia-reperfusion injury in rats
Am J Physiol Gastrointest Liver Physiol,
February 1, 2007;
292(2):
G678 - G683.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Saito, Y. Minamiya, U. Kalina, S. Saito, and J.-i. Ogawa
Effect of antithrombin III on neutrophil deformability
J. Leukoc. Biol.,
September 1, 2005;
78(3):
777 - 784.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
