Skip to main content
Log in

Response of cultured rat Kupffer cells to lipopolysaccharide

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

The effects of Salmonella abortus equi lipopolysaccharides (LPS) on pure cultures of rat Kupffer cells (Kc) were studied. In vitro, LPS is ingested by Kc and located in vacuoles and secondary lysosomes. Culture of Kc in the presence of 1–50 μg LPS/ml during 24 h did not affect the viability of the Kc as measured by trypan blue exclusion, neutral red uptake, lactate dehydrogenase leakage and cell survival and spreading. LPS treatment did not influence the ultrastructure of Kc. The exposure of Kc to LPS in vitro did not change the phagocytic actvity. Several iochemical processes were stimulated: glucose consumption, MTT-tetrazolium salt reduction, total protein synthesis and secretion of proteins. LPS activated Kc to tumoricidal activity against L929 mouse fibrosarcoma cells. In the light of the above observations, it is concluded that purified LPS is not cytotoxic for pure Kc in culture. On the contrary, LPS stimulates several biochemical and functional processes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Beutler B, Milsark IW, Cerami AC (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effects of endotoxin. Science 229: 869–871

    Google Scholar 

  • Bhatnagar R, Schade U, Rietschel ET, Decker K (1982) Involvement of prostaglandin E and adenosine 3,5-monophosphate in lipopolysaccharide-stimulated collagenase release by rat Kupffer cells. Eur J Biochem 125: 125–130

    Google Scholar 

  • Birmelin M, Karck U, Dieter P, Freudenberg N, Decker K (1986) Distribution of endotoxin and endotoxin-stimulated prostanoid production in primary cultures of rat Kupffer cells. In: Kirn A, Knook DL, Wisse E (eds) Cells of the hepatic sinusoid, vol 1. Kupffer Cell Foundation, Rijswijk, The Netherlands, pp 295–300

    Google Scholar 

  • Bouwens L, Baekeland M, de Zanger R, Wisse E (1986) Quantitation, tissue distribution and proliferation kinetics of Kupffer cells in normal rat liver. Hepatology 6: 718–722

    Google Scholar 

  • Brouwer A, De Leeuw AM, Praaning-van Dalen DP, Knook DL (1982) Isolation and culture of sinusoidal liver cells: summary of a round table discussion. In: Knook DL, Wisse E (eds) Sinusoidal liver cells. Elsevier Biomedical Press, Amsterdam, The Netherlands, pp 509–516

    Google Scholar 

  • Daemen T, Veninga A, Roerdink FH, Scherphof G (1986) In vitro activation of rat liver macrophages to tumoricidal activity by free or liposome-encapsulated muramyldipeptide. Cancer Res 46: 4330–4335

    Google Scholar 

  • Davis WB, Barsoum IS, Ramwell PW, Yeager H (1980) Human alveolar macrophages: effects of endotoxin in vitro. Inf Immun 30: 753–758

    Google Scholar 

  • Decker T, Lohmann-Matthes M, Gifford GE (1987) Cell-associated tumor necrosis factor (TNF) as a killing mechanism of activated cytotoxic macrophages. J Immunol 138: 957–962

    Google Scholar 

  • Filkins JP (1982) Role of the RES in the pathogenesis of endotoxic hypoglycemia. Circ Shock 9: 269–280

    Google Scholar 

  • Freudenberg MA, Freudenberg N, Galanos C (1982) Time course of cellular distribution of endotoxin in liver, lungs and kidneys of rats. Br J Exp Pathol 63: 56–65

    Google Scholar 

  • Freudenberg MA, Kleine B, Galanos C (1984) The fate of lipopolysaccharide in rats: Evidence for chemical alteration in the molecule. Rev Infect Dis 6: 483–487

    Google Scholar 

  • Galanos C, Lüderitz O, Westphal O (1979) Preparation and properties of a standardised lipopolysaccharide from Salmonella Abortus Equi (Novo-Pyrexal). Zentralbl Bakteriol Mikrobiol Hyg (A) 243: 226–244

    Google Scholar 

  • Lee MD, Zentella A, Pekala PH, Cerami A (1987) Effect of endotoxin-induced monokines on glucose metabolism in the muscle cell line L6. Proc Natl Acad Sci 84: 2590–2594

    Google Scholar 

  • Lüderitz O, Tanamoto K, Galanos C, McKenzie GR, Brade H, Zahringer U, Rietschel ET, Kusumoto S, Shiba T (1984) Lipopolysaccharides: Structural principles and biologic activities. Rev Infect Dis 6: 428–431

    Google Scholar 

  • Mészáros K, Lang CH, Bagby GJ, Spitzer JJ (1987) Contribution of different organs to increased glucose consumption after endotoxin administration. J Biol Chem 262: 10965–10970

    Google Scholar 

  • Maier RV, Ulevitch RJ (1981a) The induction of a unique procoagulant activity in rabbit hepatic macrophages by bacterial lipopolysaccharides. J Immunol 127: 1596–1600

    Google Scholar 

  • Maier RV, Ulevitch RJ (1981b) The response of isolated rabbit hepatic macrophages (H-Mo) to lipopolysaccharide (LPS). Circ Shock 8: 165–181

    Google Scholar 

  • Männel DN, Moore RN, Mergenhagen SE (1980) Macrophages as a source of tumoricidal activity (tumor necrotising factor). Infect Immun 30: 523–530

    Google Scholar 

  • Männel DN, Northoff H, Bauss F, Falk W (1987) Tumor necrosis factor: a cytokine involved in toxic effects of endotoxin. Rev Infect Dis 9 (suppl 5): S602-S606

    Google Scholar 

  • Mathison JC, Ulevitch RJ (1979) The clearance, tissue distribution and cellular localization of intravenously injected lipopolysaccharide in rabbits. J Immunol 123: 2133–2143

    Google Scholar 

  • Morrison DC, Ulevitch RJ (1978) The effects of bacterial endotoxins on host mediation systems. Am J Pathol 93: 527–617

    Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth 65: 55–63

    Google Scholar 

  • Netheler H (1974) Methods of measurement and instruments used. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 180–213

    Google Scholar 

  • Pabst MJ, Johnston RB (1980) Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide. J Exp Med 151: 101–114

    Google Scholar 

  • Remels L, De Baetselier PC (1987) Characterisation of 3LL-tumor variants generated by in vitro macrophage-mediated selection. Int J Cancer 39: 343–352

    Google Scholar 

  • Roobol C, Bernheim JL (1985) A novel dye reduction method for in vitro chemosensitivity testing. In: Ishigami J (ed) Recent advances in chemotherapy. University of Tokyo Press, Tokyo, pp 375–376

    Google Scholar 

  • Roubin R, Benveniste J (1985) Formation of prostaglandins, leucotrienes and PAF-acether by macrophages. Comp Immun Microbiol Infect Dis 8: 109–118

    Google Scholar 

  • Ruiter DJ, Van der Meulen J, Brouwer A, Hummel MJR, Mauw BJ, Van der Ploeg JCM, Wisse E (1981) Uptake by liver cells of endotoxin following its intravenous injection. Lab Invest 45: 38–45

    Google Scholar 

  • Shands JW, Peavy DL, Gormus BJ, McGraw J (1974) In vitro and in vivo effects of endotoxin on mouse peritoneal cells. Infect Immun 9: 106–112

    Google Scholar 

  • Stukart MJ, Rijnsent A, Roos E (1987) Induction of tumoricidal activity in isolated rat liver macrophages by liposomes containing recombinant rat γ-interferon supplemented with lipopolysaccharide or muramyldipeptide. Cancer Res 47: 3880–3885

    Google Scholar 

  • Unanue ER, Kiely J-M, Calderon J (1976) The modulation of lymphocyte functions by molecules secreted by macrophages. II. Conditions leading to increased secretion. J Exp Med 144: 155–166

    Google Scholar 

  • Van Bossuyt H, Wisse E (1986) Time course of cellular and subcellular distribution of endotoxin (with emphasis on lipid A) in rat liver. In: Imura T, Maruse S, Suzuki Y (eds) Proc XIth Int Cong on Electron Microscopy Jap Soc Electron Microscopy, Tokyo, Japan, pp 2911–2912

  • Van Bossuyt H, Wisse E (1988) Structural changes produced in Kupffer cells in the rat liver by injection of lipopolysaccharide. Cell Tissue Res 251: 205–214

    Google Scholar 

  • Yoshimura T, Matsushima K, Oppenheim JJ, Leonard EJ (1987) Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leucocytes: partial characterisation and separation from interleukin (IL1). J Immunol 139: 788–793

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Van Bossuyt, H., Desmaretz, C., Rombaut, B. et al. Response of cultured rat Kupffer cells to lipopolysaccharide. Arch Toxicol 62, 316–324 (1988). https://doi.org/10.1007/BF00332494

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00332494

Key words

Navigation