Immunosuppressants decrease neutrophil chemoattractant and attenuate ischemia/reperfusion injury of the liver in rats

被引:41
作者
Matsuda, T
Yamaguchi, Y
Matsumura, F
Akizuki, E
Okabe, K
Liang, J
Ohshiro, H
Ichiguchi, O
Yamada, S
Mori, K
Ogawa, M
机构
[1] Kumamoto Univ, Sch Med, Dept Surg 2, Kumamoto 860, Japan
[2] Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 1, Kitakyushu, Fukuoka 807, Japan
关键词
azathioprine; cyclosporine; tacrolimus; rapamycin; cytokine-induced neutrophil chemoattractant (CINC); reperfusion injury; liver; rat;
D O I
10.1097/00005373-199803000-00009
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background: Neutrophils may play an important role in the development of liver ischemia/reperfusion injury. We investigated the effects of the immunosuppressants azathioprine (AZA), cyclosporine A (CsA), tacrolimus (FK506), and rapamycin (RPM) on the expression of cytokine-induced neutrophil chemoattractant (CINC) after ischemia/reperfusion of the liver. Methods: Liver ischemia was induced in male Wistar rats by occluding the portal vein with a microvascular clip for 30 minutes. Rats received two intramuscular injections of AZA (4 mg/kg), CsA (5 mg/kg), FK506 (0.5 mg/kg), or RPM (0.5 mg/kg) 3 and 24 hours before ischemia/reperfusion of the liver. Results: Serum CMC concentrations in untreated animals increased, peaked 6 hours after reperfusion, and thereafter decreased gradually. Pretreatment with AZA, CsA, FK506, and RPM, however, inhibited the increase in serum CINC concentrations after reperfusion. CINC mRNA in liver tissue increased and peaked 3 hours after reperfusion, but was significantly lower in animals treated with AZA, CsA, FK506, and RPM. In vitro CINC production by Kupffer cells harvested from animals treated with AZA, CsA, FK506, or RPM 3 hours after reperfusion was also significantly lower than that observed in untreated animals. Both myeloperoxidase activity and the number of neutrophils accumulating in the liver 23 hours after reperfusion in animals treated with AZA, CsA, FK506, and RPM were significantly lower than in untreated animals. This correlated with lower serum aspartate transaminase, alanine transaminase, and lactate dehydrogenase levels in animals treated with AZA, CsA, FK506, and RPM 24 hours after reperfusion. Conclusion: The immunosuppressants AZA, CsA, FK506, and RPM reduce neutrophil accumulation and attenuate ischemia/reperfusion injury of the liver.
引用
收藏
页码:475 / 483
页数:9
相关论文
共 61 条
[1]   INHIBITION OF LEUKOCYTE CHEMOTAXIS BY IMMUNOSUPPRESSIVE AGENTS - SPECIFIC-INHIBITION OF LYMPHOCYTE CHEMOTAXIS BY CYCLOSPORINE [J].
ADAMS, DH ;
WANG, LF ;
NEUBERGER, JM ;
ELIAS, E .
TRANSPLANTATION, 1990, 50 (05) :845-850
[2]   FK506 inhibits human lymphocyte migration and the production of lymphocyte chemotactic factors in liver allograft recipients [J].
Adams, DH ;
Liu, Q .
HEPATOLOGY, 1996, 23 (06) :1476-1483
[3]  
Andrews P C, 1986, Methods Enzymol, V132, P369
[4]   INFLUENCE OF OXYGEN-DERIVED FREE-RADICAL SCAVENGERS ON ISCHEMIC LIVERS [J].
ATALLA, SL ;
TOLEDOPEREYRA, LH ;
MACKENZIE, GH ;
CEDERNA, JP .
TRANSPLANTATION, 1985, 40 (06) :584-590
[5]   NEUTROPHIL-ACTIVATING PEPTIDE-1 INTERLEUKIN-8, A NOVEL CYTOKINE THAT ACTIVATES NEUTROPHILS [J].
BAGGIOLINI, M ;
WALZ, A ;
KUNKEL, SL .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (04) :1045-1049
[6]   HIGH-YIELD PREPARATION OF ISOLATED RAT LIVER PARENCHYMAL CELLS - A BIOCHEMICAL AND FINE STRUCTURAL STUDY [J].
BERRY, MN ;
FRIEND, DS .
JOURNAL OF CELL BIOLOGY, 1969, 43 (03) :506-+
[7]   CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT MEDIATES NEUTROPHILIC ALVEOLITIS IN RATS - ASSOCIATION WITH NUCLEAR FACTOR KAPPA-B-ACTIVATION [J].
BLACKWELL, TS ;
HOLDEN, EP ;
BLACKWELL, TR ;
DELARCO, JE ;
CHRISTMAN, JW .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1994, 11 (04) :464-472
[8]   BIOLOGICAL EFFECTS OF CYCLOSPORIN-A - NEW ANTILYMPHOCYTIC AGENT [J].
BOREL, JF ;
FEURER, C ;
GUBLER, HU ;
STAHELIN, H .
AGENTS AND ACTIONS, 1976, 6 (04) :468-475
[9]   CALCIUM SIGNALING IN T-CELLS STIMULATED BY A CYCLOPHILIN B-BINDING PROTEIN [J].
BRAM, RJ ;
CRABTREE, GR .
NATURE, 1994, 371 (6495) :355-358
[10]   IMMUNOPHILIN FK506 BINDING-PROTEIN ASSOCIATED WITH INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR MODULATES CALCIUM FLUX [J].
CAMERON, AM ;
STEINER, JP ;
SABATINI, DM ;
KAPLIN, AI ;
WALENSKY, LD ;
SNYDER, SH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (05) :1784-1788