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01-06-2008

Platelets Promote Liver Regeneration under Conditions of Kupffer Cell Depletion after Hepatectomy in Mice

Authors: Soichiro Murata, Ryota Matsuo, Osamu Ikeda, Andriy Myronovych, Motonobu Watanabe, Katsuji Hisakura, Yoritaka Nakano, Ikuka Hashimoto, Nobuhiro Ohkohchi

Published in: World Journal of Surgery | Issue 6/2008

Abstract

Background

Platelets have been proven to promote liver regeneration after hepatectomy. Kupffer cells produce inflammatory cytokines and also promote liver regeneration. In the present study, we examined whether platelets promote liver regeneration after hepatectomy under conditions of Kupffer cell depletion.

Methods

Seventy percent hepatectomy was carried out in mice, which were subsequently divided into four groups: (1) a normal group without any treatment, (2) a Kupffer cell depleted (KD) group, (3) a thrombocytotic group, and (4) a combined thrombocytotic and Kupffer cell depleted (TKD) group. Growth kinetics in the liver regeneration, growth factors, inflammatory cytokines, and signal transduction relating to hepatocyte proliferation were analyzed.

Results

In the KD group, liver regeneration was significantly delayed compared to the normal group 48 h after hepatectomy. On the other hand, liver regeneration of the TKD group increased significantly compared to KD group, to a level that was the same as that recorded in the normal group. In the thrombocytotic group, liver regeneration increased significantly compared to the normal group. Tumor necrosis factor alpha (TNF-α) expression was lower in the KD and TKD groups than in the normal group after hepatectomy, but, in the TKD group, hepatocyte growth factor and Akt phosphorylation were higher than in the normal and KD groups.

Conclusions

After hepatectomy, liver regeneration in the Kupffer cell depleted group was delayed because of lower TNF-α expression. Platelets promote liver regeneration even under condition of Kupffer cell depletion by stimulating hepatocyte growth factor and insulin-like growth factor-1 expression, and they activate Akt.

Michalopoulos GK, DeFrances MC (1997) Liver regeneration. Science 276:60–66PubMedCrossRef

Fausto N (2000) Liver regeneration. J Hepatol 32:19–31PubMedCrossRef

Higgins GM, Anderson RM (1931) Experimental pathology of the liver. Arch Pathol 12:186–202

Murata S, Ohkohchi N, Matsuo R et al (2007) Platelets promote liver regeneration in early period after hepatectomy. World J Surg 31:808–816PubMedCrossRef

Matsuo R, Ohkohchi N, Murata S et al (2007) Platelets strongly induce hepatocyte proliferation with IGF-1 and HGF in vitro. J Surg Res (in press)

Hoshi R, Murata S, Matsuo R et al (2007) Freeze-dried platelets promote hepatocyte proliferation in mice. Cryobiology 55:255–260PubMedCrossRef

Lesurtel M, Graf R, Aleil B et al (2006) Platelet-derived serotonin mediates liver regeneration. Science 312:104–107PubMedCrossRef

Cornell RP (1985) Restriction of gut-derived endotoxin impairs DNA synthesis for liver regeneration. Am J Physiol 249: R563–R569PubMed

Streetz KL, Luedde T, Manns MP et al (2000) Interlekin 6 and liver regeneration. Gut 47:309–312PubMedCrossRef

10.

Akerman A, Cote P, Yang QS et al (1992) Antibodies to tumor necrosis factor-α inhibit liver regeneration after partial hepatectomy. Am J Physiol 263:G579–G585PubMed

11.

Katsumoto F, Miyazaki K, Nakayama F (1990) Stimulation of DNA synthesis in hepatocytes by Kupffer cells after partial hepatectomy. Hepatology 9:405–410CrossRef

12.

Higashitsuji H, Arii S, Furutani M et al (1995) Expression of cytokine genes during liver regeneration after partial hepatectomy in the rat. J Surg Res 58:267–274PubMedCrossRef

13.

Granado M, Martini AI, Priego T et al (2006) Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression. J Endocrinol 188:503–511PubMedCrossRef

14.

Ping C, Xiaoling D, Jin Z (2006) Hepatic sinusoidal endothelial cells promote hepatocyte proliferation early after partial hepatectomy in rats. Arch Med Res 37:576–583PubMedCrossRef

15.

Van Rooijen N, Kors N, Van de Ende M, Dijkstra CD (1990) Depletion and repopulation of macrophages in spleen and liver of rat after intravenous treatment with liposome-encapsulated dichloromethylene diphosphonate. Cell Tissue Res 260:215–222PubMedCrossRef

16.

Van Rooijen N, Sanders A (1994) Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods 174:83–93PubMedCrossRef

17.

Baustica AP, Skrepnik N, Niesman MR et al (1994) Elimination of macrophages by liposome encapsulated dichloromethylene diphosphonate suppresses the endotoxin-induced priming of Kupffer cells. J Leukoc Biol 55:321–327

18.

Shibuya K, Akahori H, Takahashi K et al (1998) Multilineage hematopoietic recovery by a single injection of pegylated recombinant human megakaryocyte growth and development factor in myelosuppressed mice. Blood 91:37–45PubMed

19.

Skomorovski K, Harpak H, Ianovski A et al (2003) New TPO treatment schedules of increased safety and efficacy: pre-clinical validation of a thrombopoiesis simulation model. Br J Haematol 123:683–691PubMedCrossRef

20.

Ju C, Pohl LR (2001) Immunohistochemical detection of protein adducts of 2,4-dinitrochlorobenzene in antigen presenting cells and lymphocytes after oral administration to mice: lack of a role of Kupffer cells in oral tolerance. Chem Res Toxicol 14:1209–1217PubMedCrossRef

21.

Nagata Y, Nagahisa H, Aida Y et al (1995) Thrombopoietin induces megakaryocyte differentiation in hematopoietic progenitor FDC-P2 cells. J Biol Chem 270:19673–19675PubMedCrossRef

22.

Nagata Y, Shozaki Y, Nagahisa H et al (1997) Serum thrombopoietin level is not regulated by transcription but by the total counts of both megakaryocytes and platelets during thrombocytopenia and thrombocytosis. Thromb Haemost 77:808–814PubMed

23.

Meijer C, Wiezer MJ, Diehl AM et al (2000) Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy. Liver 20:66–77PubMedCrossRef

24.

Kamii K, Tanaka T, Komatsu Y et al (19960 Role of macrophages in regeneration of liver. Dig Dis Sci 41:1939–1946PubMedCrossRef

25.

Abshagen K, Eipel C, Kalff JC et al (2007) Loss of NF-{kappa} B activation in Kupffer cell-depleted mice impairs liver regeneration after partial hepatectomy. Am J Physiol Gastrointest Liver Physiol 292:G1570–1577PubMedCrossRef

26.

Nakamura M, Shibasaki M, Nitta Y et al (1998) Translocation of platelets into Disse space and their entry into hepatocytes in response to lipopolysaccharides, interleukin-1 and tumour necrosis factor: the role of Kupffer cells. J Hepatol 28:991–999PubMedCrossRef

27.

Endo Y, Nakamura M (1992) The effect of lipopolysaccharide, interleukin-1 and tumour necrosis factor on the hepatic accumulation of 5-hydroxytryptamine and platelets in the mouse. Br J Pharmacol 105:613–619PubMed

28.

Ohtaki Y, Shimauchi H, Yokochi T et al (2003) In vivo platelet response to lipopolysaccharide in mice: proposed method for evaluating new antiplatelet drugs. Thromb Res 108:303–309CrossRef

29.

Zhu X, Zellweger R, Zhu X et al (1995) Cytokine gene expression in splenic macrophages Kupffer cells following hemorrhage. Cytokine 7:8–14PubMedCrossRef

30.

Nagata Y, Tanaka K, Orita K (1994) Endotoxin-induced liver injury after extended hepatectomy and the role of Kupffer cells in the rat. Surg Today 24:441–448PubMedCrossRef

31.

Yamada Y, Kirillova I, Peschon JJ et al (1997) Initiation of liver growth by tumor necrosis factor: deficient liver regeneration in mice lacking type I tumor necrosis factor receptor. Proc Natl Acad Sci USA 94:1441–1446PubMedCrossRef

32.

Diehl AM, Yin M, Fleckenstein J et al (1994) Tumor necrosis factor-α induces c-jun during the regenerative response to liver injury. Am J Physiol 267:G552–G561PubMed

33.

Devi SS, Mehendale HM (2005) The role of NF-kappa B signaling in impaired liver tissue repair in thioacetamide-treated type I diabetic rats. Eur J Pharmacol 523:127–136PubMedCrossRef

34.

Akerman P, Cote P, Yang S et al (1992) Antibodies to tumor necrosis factor-α inhibit liver regeneration after partial hepatectomy. Am J Physiol 263:G579–G585PubMed

35.

Yamada Y, Webber EM, Kirillova I et al (1998) Analysis of liver regeneration in mice lacking type 1 or type 2 tumor necrosis factor receptor: requirement for type 1 but not type 2 receptor. Hepatology 28:959–970PubMedCrossRef

36.

Libermann TA, Baltimore D (1990) Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol 10:2327–2334PubMed

37.

Yamada Y, Fausto N (1998) Deficient liver regeneration after carbon tetrachloride injury in mice lacking type 1 but not type 2 tumor necrosis factor receptor. Am J Pathol 152: 577–1589

38.

Cressman DE, Greenbaum LE, Haber BA et al (1995) Rapid activation of the STAT3 transcription complex in liver regeneration. Hepatology 21:1443–1449PubMed

39.

Cressman DE, Greenbaum LE, DeAngelis RA et al (1996) Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice. Science 274:1379–1383PubMedCrossRef

40.

Oikawa K, Ohkohchi N, Sato M et al (2002) Kupffer cells play an important role in the cytokine production and activation of nuclear factors of liver grafts from non-heart-beating donors. Transpl Int 15:397–405PubMedCrossRef

41.

Ohkohchi N (2002) Mechanisms of preservation and ischemic/reperfusion injury in liver transplantation. Transplant Proc 34:2670–2673PubMedCrossRef

42.

Yoshizumi T, Yonemitsu Y, Ikeda Y et al (2006) Tumor necrosis factor-a antisense transfer remarkably improves hepatic graft viability. Liver Int 26:451–456PubMedCrossRef

43.

Von Frankenberg M, Golling M, Mehrabi A et al (2003) Donor pretreatment with gadolinium chloride improves early graft function and survival after porcine liver transplantation. Transplant Int 16:806–813CrossRef

Title: Platelets Promote Liver Regeneration under Conditions of Kupffer Cell Depletion after Hepatectomy in Mice
Authors: Soichiro Murata
Ryota Matsuo
Osamu Ikeda
Andriy Myronovych
Motonobu Watanabe
Katsuji Hisakura
Yoritaka Nakano
Ikuka Hashimoto
Nobuhiro Ohkohchi
Publication date: 01-06-2008
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 6/2008
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-008-9493-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Platelets Promote Liver Regeneration under Conditions of Kupffer Cell Depletion after Hepatectomy in Mice

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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