Cover Page

Cite item


Bacterial lipopolysaccharides (LPS) are highly toxic molecules released during the lysis of bacterial cells. They play important role in the pathogenesis of sepsis, and can contaminate pharmaceuticals, so removing them from aqueous solutions and biological fluids is an extremely important task. Structure of LPS and its toxicity for various animals are presented in this review. Various low- and high-molecular ligands, suitable for efficient binding and removal LPS from solutions are studied and demonstrated. The main attention is paid to the relationship between the chemical structure of the ligand and its ability to form strong complexes with LPS and the principles of creating selective ligands for the depyrogenation of pharmaceutical substances and the creation of hemoperfusion columns for the sepsis therapy.

About the authors

M. N. Kopitsyna

JSC Advanced Medical Technologies

Author for correspondence.
Russian Federation

A. S. Morozov

JSC Advanced Medical Technologies; Lomonosov Moscow State University

Russian Federation

I. V. Bessonov

JSC Advanced Medical Technologies; Lomonosov Moscow State University

Russian Federation

V. M. Pisarev

V.A.Negovsky Research Institute of General Reanimatology

Russian Federation

E. S. Lobakova

Lomonosov Moscow State University

Russian Federation

O. V. Bukharin

Institute of Cellular and Intracellular Symbiosis

Russian Federation


  1. Государственная фармакопея Российской Федерации. XII издание. Ч. 1. гл. 27 Бактериальные эндотоксины (ОФС 42-0062-07). М.: научный центр экспертизы средств медицинского применения. 2007: с. 128-136.
  2. Красоткина Ю.В., Кустова П.А., Бессонов И.В., Морозов А.С., Копицына М.Н., Карелина Н.В., Нуждина А.В. «Эндосорб» - новый эффективный сорбент для очистки растворов фармацевтических белков от эндотоксинов. V съезд биофизиков России. Ростов-на-Дону; 2015: с. 208.
  3. Морозов А.С., Бессонов И.В., Нуждина А.В., Писарев В.М. Сорбенты для экстракорпорального удаления токсических веществ и молекул с нежелательной биологической активностью (обзор). Общая реаниматология. 2016, 12 (6): 82-107.
  4. Anisimova N. Yu. Immunological pathogenesis of sepsis and use of hemosorption for treatment of cancer patients with sepsis. New York: Nova Science Publishers Inc, 2014: p. 57-114.
  5. Anspach F. B. Membrane adsorbers for selective endotoxin removal from protein solutions. Process Biochemistry. 2000, 35: 1005-1012.
  6. Anspach F.B. Endotoxin removal by affinity sorbents. J. Biochem. Biophys. Methods. 2001, 49(1-3): 665-681.
  7. Anspach ЕВ., Hilbeck О. Removal of endotoxins by affinity sorbents. J. Chromatogr. A. 1995, 711 (1): 81-92.
  8. Berezi I., Bertok L., Bereznai T. Comparative studies on the toxicity of Escherichia coli lipopolysaccharide endotoxin in various animal species. Can. J. Microbiol. 1966, 12 (5): 1070-1071.
  9. Bone R.C. Gram-negative sepsis: a dilemma of modem medicine. Clin. Microbiol. Rev. 1993, 6(1): 57-68.
  10. Caroff M., Karibian D. Structure ofbacterial lipopolysaccharides. Carbohydr. Res. 2003, 338 (23): 2431-2447.
  11. Clark I. A. Correlation between susceptibility to malaria and babesia parasites and to endotox-icity. Trans. R. Soc. Trop. Med. Hyg. 1982, 76 (1): 4-7.
  12. Copeland S., Warren H.S., Lowry S.F. et al. Inflammation and the host response to injury investigators. Acute inflammatory response to endotoxin in mice and humans. Clin. Diagn. Lab. Immunol. 2005, 12 (1): 60-67.
  13. Cruz D.N., Antonelli M., Fumagalli R. et al. Early use of polymyxin b hemoperfusion in abdominal septic shock. JAMA. 2009, 301 (23): 2445-2452.
  14. Cutuli S.L., Artigas A., Fumagalli R. et al. EUPHAS 2 Collaborative Group. Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry. Ann. Intensive Care. 2016, 6(1): 77.
  15. Damais C., Jupin C., Parant M., Chedid L. Induction of human interleukin-1 production by polymyxin B. J. Immunol. Methods. 1987, 101 (1): 51-56.
  16. David S.A. Towards a rational development of anti-endotoxin agents: novel approaches to sequestration ofbacterial endotoxins with small molecules. J. Mol. Recognit. 2001, 14 (6): 370-387.
  17. Goodwin M.H., Stapleton T.K. The course of natural and induced infections of Plasmodium joyrides in Sceloporus undulatus undulatus. Am. J. Trop. Med. Hyg. 1952, 1 (5): 773-783.
  18. Hanora A., Plieva F.M., Hedstrom M. et al. Capture ofbacterial endotoxins using a superma-croporous monolithic matrix with immobilized polyethyleneimine, lysozyme or polymyxin B. J. Biotechnol. 2005, 118 (4): 421-433.
  19. Hou K.C., Zaniewski R. Depyrogenation by endotoxin removal with positively charged depth filter cartridge. J. Parenter. Sci. Technol. 1990, 44(4): 204-209.
  20. Jansson P.-E. The chemistry of O-polysaccharide chains in bacterial lipopolysaccharides. In: Brade H. et al. (eds.). Endotoxin in health and disease. New York: Medical Directions Incorporation; 1999: p. 155-178.
  21. Karplus T.E., Ulevitch R.J., Wilson C.B. A new method for reduction of endotoxin contaminations from protein solutions. J. Immunol. Methods. 1987, 105 (2): 211-220.
  22. Kastowsky M., Gutberlet T, Bradaczek H. Molecular modelling of the three-dimensional structure and conformational flexibility of bacterial lipopolysaccharide. J. Bacteriol. 1992,174 (14): 4798-4806.
  23. Kim Y.B., Watson D.W. Role of antibodies in reactions to gram-negative bacterial endotoxins. Ann. N. Y. Acad. Sci. 1966, 133 (2): 727-745.
  24. Kumar A. An alternate pathophysiologic paradigm of sepsis and septic shock. Virulence. 2014, 5 (1): 80-97.
  25. Legallais C., Anspach F.B., Bueno S.M.A. et al. Strategies for the depyrogenation of contaminated IgG solutions by histidine-immobilized hollow fiber membrane. J. Chromatogr. B. Biomed. Sci Appl. 1997, 691 (1): 33-41.
  26. Magalhaes P.O., Lopes A.M., Mazzola P.G. et al. Methods of endotoxin removal from biological preparations: a review. J. Pharm. Pharm. Sci. 2007, 10 (3): 388-404.
  27. Malik D.J., Webb C., Holdich R.G. et al. Synthesis and characterization of size-selective nanoporous polymeric adsorbents for blood purification. Sep. Purif. Technol. 2009, 66 (3): 578-585.
  28. Mares J., Kumaran S., Gobbo M., Zerbe O. Interactions of lipopolysaccharide and polymyxin studied by NMR spectroscopy. J. Biol. Chem. 2009, 284(17): 11498-11506.
  29. Minobe S., Watanabe T, Sato T. et al. Preparation of adsorbents for pyrogen adsorption. J. Chromatogr. 1982, 248:401-408.
  30. Moran A.P, Rietschel E.T., Kosunen T.U., Zahringer U. Chemical characterization of Campylobacter jejuni lipopolysaccharides containing N-acetylneuraminic acid and 2,3-di-amino -2,3-dideoxy-D-glucose. J. Bacteriol. 1991, 173 (2): 618-626.
  31. Morozov A.S., Kopitsyna M.N., Bessonov I.V. et al. A selective sorbent for removing bacterial endotoxins from blood. Russ. J. Phys. Chem. A 2016, 90 (12): 2465-2470.
  32. Mueller M., Lindner B., Kusumoto S. et al. Aggregates are the biologically active units of endotoxin. J. Biol. Chem. 2004, 279 (25): 26307-26313.
  33. Newton B.A. The properties and mode of action of the polymyxins. Bacteriol. Rev. 1956, 20 (1): 14-27.
  34. Petsch D., Beeskow T.C., Anspach F.B., Deckwer W.-D. Membrane adsorbers for selective removal ofbacterial endotoxin. J. Chromatogr. B. Biomed. Sci. Appl. 1997, 693 (1): 79-91.
  35. Raetz C.R., Whitfield C. Lipopolysaccharide endotoxins. Annu. Rev. Biochem. 2002,71:635-700.
  36. Raetz C.R.H. Biochemistry of endotoxins. Annu. Rev. Biochem. 1990, 59: 129-170.
  37. Raetz C.R.H. Escherichia coli and Salmonella. In: Niedhardt EC. et al. (eds). Cellular and molecular biology. Washington, D.C.: American Society for Microbiology; 1996, p. 1035-1063.
  38. Reddin J.L., Starzecki B., Spink W.W. Comparative hemodynamic and humoral responses of puppies and adult dogs to endotoxin. Am. J. Physiol. 1966, 210 (3): 540-544.
  39. Rubenstein M., Mulholland J.H., Jeffery G.M., Wolff S.M. Malaria induced endotoxin tolerance. Exp. Biol. Med. (Maywood). 1965, 118 (1): 283-287.
  40. Sauter C., Wolfensberger C. Interferon in human serum after injection of endotoxin. Lancet. 1980, 316(8199): 852-853.
  41. Schmidt L.H. Plasmodium falciparum and Plasmodium vivax infections in the owl monkey (Aotus trivirgatus) 1. The courses of untreated infections. Am. J. Trop. Med. Hyg. 1978,27(4): 671-702.
  42. Seydel U., Brandenburg K., Koch M.H., Rietschel E.T. Supramolecular structure of lipopolysaccharide and free lipid A under physiological conditions as determined by synchrotron small-angle X-ray diffraction. Eur. J. Biochem. 1989, 186 (1-2): 325-332.
  43. Shoji H. Extracorporeal endotoxin removal for the treatment of sepsis: endotoxin adsorption cartridge (Toraymyxin). Ther Apher Dial. 2003, 7: 108-114.
  44. Silipo A., Molinaro A. Lipid A structure. In: Knirel Y. A., Valvano M. A. (eds.). Bacterial li-popolysaccharides. Structure, chemical, synthesis, biogenesis and interaction with host cells. N.Y.: Springer; 2011, p. 1-20.
  45. Silverman M.H., Ostro J. Bacterial endotoxin in human disease. How advances in understanding the role of Gram-negative bacteria and endotoxin in infectious diseases and complications may improve the development of diagnostic and treatment options, Berkeley: XOMA LLC; 1999: 1-30.
  46. Smith C.E. Bacterial and Mycotic Infections of Man. Am. J. Public. Health. 1953, 43 (10): 1344-1345.
  47. Srimal S., Surolia N., Balasubramanian S., Surolia A. Titration calorimetric studies to elucidate the specificity of the interaction of polymyxin В with lipopolysaccharides and lipid A. Biochem. J. 1996,315: 679-686.
  48. Talmadge K.W., SiebertC.J. Efficient endotoxin removal with a new sanitizable affinity column: affi-prep polymyxin. J. Chromatogr. 1989, 476: 175-185.
  49. Vaara M., Nikaido H. Outer membrane organization. In: Rietschel E. T. (ed.). Handbook of Endotoxin. Amsterdam: Elsevier; 1984: p. 1-45.
  50. Wilkinson S.G. Bacterial lipopolysaccharides - themes and variations. Prog. Lipid Res. 1996, 35 (3): 283-343.

Copyright (c) 2017 Kopitsyna M.N., Morozov A.S., Bessonov I.V., Pisarev V.M., Lobakova E.S., Bukharin O.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС77-75442 от 01.04.2019 г.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies