Preview

Вопросы гематологии/онкологии и иммунопатологии в педиатрии

Расширенный поиск

Cовременное представление о системе комплемента

https://doi.org/10.24287/1726-1708-2019-18-3-130-144

Полный текст:

Аннотация

Комплемент представляет собой часть системы иммунитета, обеспечивающую защиту клеток организма от патогенных клеток и частиц. Она запускается при обнаружении вторжения патогенов. Результаты многочисленных исследований привели к осознанию огромной роли этой системы в поддержании нормального функционирования организма. В данном обзоре описано современное представление о работе системы комплемента.

Об авторах

С. С. Шахиджанов
ФГБУН «Центр теоретических проблем физико-химической фармакологии» РАН
Россия

Шахиджанов Сослан Сергеевич, научный сотрудник

119991, Москва, ул. Косыгина, 4



А. Е. Филиппова
ФГБУН «Центр теоретических проблем физико-химической фармакологии» РАН
Россия
Москва


А. А. Бутылин
ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»
Россия
Москва


Ф. И. Атауллаханов
ФГБУН «Центр теоретических проблем физико-химической фармакологии» РАН; ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»; ФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России; ФГАОУ ВО «Московский физико-технический институт (государственный университет)»
Россия

Москва

 



Список литературы

1. Cruse J.M., Lewis R.E. The Complement System. In: Cruse JM, Lewis RE, editors. Atlas of Immunology [Internet]. Berlin, Heidelberg: Springer Berlin Heidelberg 1999 [cited 2019 Feb 24]. p. 207–24. Available from: https://doi.org/10.1007/978-3-662-11196-3_11

2. Nonaka M. Evolution of the Complement System. In: Anderluh G, Gilbert R, editors. MACPF/CDC Proteins – Agents of Defence, Attack and Invasion [Internet]. Dordrecht: Springer Netherlands 2014 [cited 2019 Feb 24]. p. 31–43. (Subcellular Biochemistry). Available from: https://doi.org/10.1007/978-94-017-8881-6_3

3. Lachmann P.J. Chapter 4 – The Amplification Loop of the Complement Pathways. In: Alt FW, editor. Advances in Immunology [Internet]. Academic Press 2009 [cited 2018 Feb 17]. p. 115–49. (Advances in Immunology; vol. 104). Available from: http://www.sciencedirect.com/science/article/pii/S0065277608040042

4. Fujita T. Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol 2002 May; 2 (5): 346–53.

5. Murphy K., Weaver C. Janeway’s immunobiology. 9th edition. New York, NY: Garland Science/Taylor & Francis Group, LLC; 2016. 904 p.

6. Holers V.M. Complement and its receptors: new insights into human disease. Annu Rev Immunol 2014; 32: 433–59.

7. Merle N.S., Church S.E., Fremeaux-Bacchi V., Roumenina L.T. Complement System Part I – Molecular Mechanisms of Activation and Regulation. Front Immunol [Internet] 2015 [cited 2018 Mar 27]; 6. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2015.00262/full

8. Zipfel P.F., Skerka C. Complement regulators and inhibitory proteins. Nat Rev Immunol 2009 Oct; 9 (10): 729–40.

9. Brodsky R.A. Paroxysmal nocturnal hemoglobinuria. Blood 2014 Oct 30; 124 (18): 2804–11.

10. Risitano A.M. Paroxysmal nocturnal hemoglobinuria and other complement-mediated hematological disorders. Immunobiology 2012 Nov 1; 217 (11): 1080–7.

11. Rother R.P., Rollins S.A., Mojcik C.F., Brodsky R.A., Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotech 2007 Nov; 25(11): 1256–64.

12. Devalet B., Mullier F., Chatelain B., Dogné J.-M., Chatelain C. Pathophysiology, diagnosis, and treatment of paroxysmal nocturnal hemoglobinuria: a review. Eur J Haematol 2015 Sep 1; 95 (3): 190–8.

13. Kavanagh D., Goodship T.H., Richards A. Atypical Hemolytic Uremic Syndrome. Semin Nephrol 2013 Nov; 33 (6): 508–30.

14. Pettigrew H.D., Teuber S.S., Gershwin M.E. Clinical Significance of Complement Deficiencies. Annals of the New York Academy of Sciences 2009; 1173 (1): 108–23.

15. Trouw L.A., Pickering M.C., Blom A.M. The complement system as a potential therapeutic target in rheumatic disease. Nature Reviews Rheumatology 2017 Sep; 13 (9): 538–47.

16. Mortensen S.A., Sander B., Jensen R.K., Pedersen J.S., Golas M.M. Jensenius J.C., et al. Structure and activation of C1, the complex initiating the classical pathway of the complement cascade. PNAS 2017 Jan 31; 114 (5): 986–91.

17. Gaboriaud C., Thielens N.M., Gregory L.A., Rossi V., Fontecilla-Camps J.C., Arlaud G.J. Structure and activation of the C1 complex of complement: unraveling the puzzle. Trends Immunol 2004 Jul; 25 (7): 368–73.

18. Duncan A.R., Winter G. The binding site for C1q on IgG. Nature 1988 Apr 21; 332 (6166): 738–40.

19. Perkins S.J., Nealis A.S., Sutton B.J., Feinstein A. Solution structure of human and mouse immunoglobulin M by synchrotron X-ray scattering and molecular graphics modelling. A possible mechanism for complement activation. J Mol Biol 1991 Oct 20; 221 (4): 1345–66.

20. Shulman M.J., Collins C., Pennell N., Hozumi N. Complement activation by IgM: evidence for the importance of the third constant domain of the mu heavy chain. Eur J Immunol 1987 Apr; 17 (4): 549–54.

21. Chen F.H., Arya S.K., Rinfret A., Isenman D.E., Shulman M.J., Painter R.H. Domain-switched mouse IgM/IgG2b hybrids indicate individual roles for C mu 2, C mu 3, and C mu 4 domains in the regulation of the interaction of IgM with complement C1q. J Immunol 1997 Oct 1; 159 (7): 3354–63.

22. Weiner E.M. On the Interaction of the First Complement Component C1 and its Subunit Clq with Solid-Phase IgM Immune Complexes. Scandinavian Journal of Immunology 1988; 28 (4): 425–30.

23. Feinstein A., Richardson N.E., Gorick B.D., Hughes-Jones N.C. Immunoglobulin M Conformational Change is a Signal for Complement Activation. In: Celada F., Schumaker V.N., Sercarz E.E., ed. Protein Conformation as an Immunological Signal [Internet]. Boston, MA: Springer US; 1983 [cited 2019 Feb 24]. p. 47–57. Available from: https://doi.org/10.1007/978-1-4613-3778-2_6

24. Diebolder C.A., Beurskens F.J., de Jong R.N., Koning R.I., Strumane K., Lindorfer M.A., et al. Complement Is Activated by IgG Hexamers Assembled at the Cell Surface. Science 2014 Mar 14; 343 (6176): 1260–3.

25. Wang G., de Jong R.N., van den Bremer E.T.J., Beurskens F.J., Labrijn A.F., Ugurlar D., et al. Molecular Basis of Assembly and Activation of Complement Component C1 in Complex with Immunoglobulin G1 and Antigen. Molecular Cell 2016 Jul 7; 63 (1): 135–45.

26. Claus D.R., Siegel J., Petras K., Osmand A.P., Gewurz H. Interactions of C-reactive protein with the first component of human complement. J Immunol 1977 Jul; 119 (1): 187–92.

27. Almitairi J.O.M., Venkatraman Girija U., Furze C.M., Simpson-Gray X., Badakshi F., Marshall J.E., et al. Structure of the C1r-C1s interaction of the C1 complex of complement activation. PNAS USA 2018 Jan 23; 115 (4): 768–73.

28. Ricklin D., Reis E.S., Lambris J.D. Complement in disease: a defence system turning offensive. Nat Rev Nephrol 2016 Jul; 12 (7): 383–401.

29. Gaboriaud C., Frachet P., Thielens N., Arlaud G. The Human C1q Globular Domain: Structure and Recognition of Non-Immune Self Ligands. Front Immunol [Internet] 2012 [cited 2018 Mar 27]; 2. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2011.00092/full

30. Law S.K.A., Dodds A.W. The internal thioester and the covalent binding properties of the complement proteins C3 and C4. Protein Science 1997 Feb 1; 6 (2): 263–74.

31. Campbell R.D., Dodds A.W., Porter R.R. The binding of human complement component C4 to antibody-antigen aggregates. Biochem J 1980 Jul 1; 189 (1): 67–80.

32. Vogt W., Hinsch B., Schmidt G., von Zabern I. Function of the activated fourth component of complement (C4b) in activation of C2. FEBS Letters 1982 Aug 2; 144 (2): 195–8.

33. Fishelson Z., Müller-Eberhard H.J. C3 convertase of human complement: enhanced formation and stability of the enzyme generated with nickel instead of magnesium. J Immunol 1982 Dec 1; 129 (6): 2603–7.

34. Rawal N., Pangburn M.K. Formation of High Affinity C5 Convertase of the Classical Pathway of Complement. J Biol Chem 2003 Oct 3; 278 (40): 38476–83.

35. Sim R.B., Twose T.M., Paterson D.S., Sim E. The covalent-binding reaction of complement component C3. Biochem J 1981 Jan 1; 193 (1): 115–27.

36. Law S.K., Lichtenberg N.A., Levine R.P. Covalent binding and hemolytic activity of complement proteins. PNAS 1980 Dec 1; 77 (12): 7194–8.

37. Law S.K., Lichtenberg N.A., Holcombe F.H., Levine R.P. Interaction between the labile binding sites of the fourth (C4) and fifth (C5) human complement proteins and erythrocyte cell membranes. J Immunol 1980 Aug 1; 125 (2): 634–9.

38. Muller-Eberhard H.J. The Membrane Attack Complex of Complement. Ann Rev Immunol 1986; 4 (1): 503–28.

39. Preissner K.T., Podack E.R., Müller-Eberhard H.J. The membrane attack complex of complement: relation of C7 to the metastable membrane binding site of the intermediate complex C5b-7. J Immunol 1985 Jul; 135 (1): 445–51.

40. Hadders M.A., Beringer D.X., Gros P. Structure of C8-MACPF Reveals Mechanism of Membrane Attack in Complement Immune Defense. Science 2007 Sep 14; 317 (5844): 1552–4.

41. Serna M., Giles J.L., Morgan B.P., Bubeck D. Structural basis of complement membrane attack complex formation. Nature Communications 2016 Feb 4; 7: ncomms10587.

42. Sharp T.H., Koster A.J., Gros P. Heterogeneous MAC Initiator and Pore Structures in a Lipid Bilayer by Phase-Plate Cryo-electron Tomography. Cell Reports 2016 Apr 5; 15 (1): 1–8.

43. Beltrame M.H., Catarino S.J., Goeldner I., Boldt A.B.W., de Messias-Reason I.J. The Lectin Pathway of Complement and Rheumatic Heart Disease. Front Pediatr [Internet]. 2015 [cited 2019 Feb 25]; 2. Available from: https://www.frontiersin.org/articles/10.3389/fped.2014.00148/full

44. Héja D., Kocsis A., Dobó J., Szilágyi K., Szász R., Závodszky P., et al. Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2. PNAS USA 2012 Jun 26; 109 (26): 10498–503.

45. Degn S.E., Kjaer T.R., Kidmose R.T., Jensen L., Hansen A.G., Tekin M., et al. Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes. PNAS USA 2014 Sep 16; 111 (37): 13445–50.

46. Pangburn M.K., Müller-Eberhard H.J. Initiation of the alternative complement pathway due to spontaneous hydrolysis of the thioester of C3. Ann N Y Acad Sci 1983; 421: 291–8.

47. Pangburn M.K., Schreiber R.D., Müller-Eberhard H.J. Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous hydrolysis of the putative thioester in native C3. J Exp Med 1981 Sep 1; 154 (3): 856–67.

48. Isenman D.E., Kells D.I.C., Cooper N.R., Mueller-Eberhard H.J., Pangburn M.K. Nucleophilic modification of human complement protein C3: correlation of conformational changes with acquisition of C3b-like functional properties. Biochemistry 1981 Jul 1; 20 (15): 4458–67.

49. Li K., Gor J., Perkins S.J. Self-association and domain rearrangements between complement C3 and C3u provide insight into the activation mechanism of C3. Biochemical J 2010 Oct 1; 431 (1): 63–72.

50. Sim R.B., Laich A. Serine proteases of the complement system. Biochem Soc Trans 2000 Oct; 28 (5): 545–50.

51. Pangburn M.K., Müller-Eberhard H.J. The C3 convertase of the alternative pathway of human complement. Enzymic properties of the bimolecular proteinase. Biochem J 1986 May 1; 235 (3): 723–30.

52. Rawal N., Pangburn M.K. Formation of High-Affinity C5 Convertases of the Alternative Pathway of Complement. J Immunol 2001 Feb 15; 166 (4): 2635–42.

53. Ferreira V.P., Pangburn M.K., Cortés C. Complement control protein factor H: The good, the bad, and the inadequate. Mol Immunol 2010 Aug; 47 (13): 2187–97.

54. Kazatchkine M.D., Nydegger U.E. The human alternative complement pathway: biology and immunopathology of activation and regulation. Prog Allergy 1982; 30: 193–234.

55. Pangburn M.K., Müller-Eberhard H.J. Complement C3 convertase: Cell surface restriction of 1H control and generation of restriction on neuraminidase-treated cells. PNAS USA 1978 May; 75 (5): 2416–20.

56. Blaum B.S., Hannan J.P., Herbert A.P., Kavanagh D., Uhrín D., Stehle T. Structural basis for sialic acid–mediated self-recognition by complement factor H. Nat Chem Biol 2015 Jan; 11 (1): 77–82.

57. Wu J., Wu Y.-Q., Ricklin D., Janssen B.J.C., Lambris J.D., Gros P. Structure of complement fragment C3b–factor H and implications for host protection by complement regulators. Nat Immunol 2009 Jul; 10 (7): 728–33.

58. Kajander T., Lehtinen M.J., Hyvärinen S., Bhattacharjee A., Leung E., Isenman D.E., et al. Dual interaction of factor H with C3d and glycosaminoglycans in host–nonhost discrimination by complement. PNAS 2011 Feb 15; 108 (7): 2897–902.

59. Morgan H.P., Schmidt C.Q., Guariento M., Blaum B.S., Gillespie D., Herbert A.P., et al. Structural basis for engagement by complement factor H of C3b on a self surface. Nat Struct Mol Biol 2011 Apr; 18 (4): 463–70.

60. Kopp A., Hebecker M., Svobodová E., Józsi M. Factor H: A Complement Regulator in Health and Disease, and a Mediator of Cellular Interactions. Biomolecules 2012 Feb 7; 2 (1): 46–75.

61. Berends E.T.M., Gorham R.D., Ruyken M., Soppe J.A., Orhan H., Aerts P.C., et al. Molecular insights into the surface-specific arrangement of complement C5 convertase enzymes. BMC Biology 2015; 13: 93.

62. Jore M.M., Johnson S., Sheppard D., Barber N.M., Li Y.I., Nunn M.A., et al. Structural basis for therapeutic inhibition of complement C5. Nat Struct Mol Biol 2016 May; 23 (5): 378–86.

63. Fearon D.T., Austen K.F. Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase. J Exp Med 1975 Oct 1; 142 (4): 856–63.

64. Kemper C., Atkinson J.P., Hourcade D.E. Properdin: emerging roles of a pattern-recognition molecule. Ann Rev Immunol 2010; 28: 131–55.

65. Spitzer D., Mitchell L.M., Atkinson J.P., Hourcade D.E. Properdin Can Initiate Complement Activation by Binding Specific Target Surfaces and Providing a Platform for De Novo Convertase Assembly. J Immunol 2007 Aug 15;179 (4): 2600–8.

66. Harboe M., Mollnes T.E. The alternative complement pathway revisited. Journal of Cellular and Molecular Medicine 2008 Aug 1;12 (4): 1074–84.

67. Hill A., DeZern A.E., Kinoshita T., Brodsky R.A. Paroxysmal nocturnal haemoglobinuria. Nature Reviews Disease Primers 2017 May 18; 3: nrdp201728.

68. Jokiranta T.S. HUS and atypical HUS. Blood 2017 May 25; 129 (21): 2847–56.

69. Sim R.B., Arlaud G.J., Colomb M.G. Kinetics of reaction of human C1-inhibitor with the human complement system proteases C1r and C1s. Biochimica et Biophysica Acta (BBA) Enzymology 1980 Apr 11; 612 (2): 433–49.

70. Nilsson T., Wiman B. Kinetics of the Reaction between Human C1-Esterase Inhibitor and C1r or C1s. Eur J Biochemistry 1983 Jan 1;129 (3): 663–7.

71. Davis A.E., Lu F., Mejia P. C1 inhibitor, a multi-functional serine protease inhibitor. Thromb Haemost 2010 Nov; 104 (5): 886–93.

72. Ziccardi R.J. A new role for C-1-inhibitor in homeostasis: control of activation of the first component of human complement. J Immunol 1982 Jun 1; 128 (6): 2505–8.

73. Paréj K., Dobó J., Závodszky P., Gál P. The control of the complement lectin pathway activation revisited: both C1-inhibitor and antithrombin are likely physiological inhibitors, while 2-macroglobulin is not. Mol Immunol 2013 Jul; 54 (3–4): 415–22.

74. Presanis J.S., Hajela K., Ambrus G., Gál P., Sim R.B. Differential substrate and inhibitor profiles for human MASP-1 and MASP-2. Mol Immunol 2004 Feb; 40 (13): 921–9.

75. Blom A.M., Zadura A.F., Villoutreix B.O., Dahlbäck B. Positively charged amino acids at the interface between α-chain CCP1 and CCP2 of C4BP are required for regulation of the classical C3-convertase. Mol Immunol 2000 Jun 1; 37 (8): 445–53.

76. Ziccardi R.J., Dahlback B., Müller-Eberhard H.J. Characterization of the interaction of human C4b-binding protein with physiological ligands. J Biol Chem 1984 Nov 25; 259 (22): 13674–9.

77. Roversi P., Johnson S., Caesar J.J.E., McLean F., Leath K.J., Tsiftsoglou S.A., et al. Structural basis for complement factor I control and its disease-associated sequence polymorphisms. PNAS 2011 Aug 2; 108 (31): 12839–44.

78. Pangburn M.K., Schreiber R.D., Müller-Eberhard H.J. Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution. Journal of Experimental Medicine 1977 Jul 1; 146 (1): 257–70.

79. Lambris J.D., Lao Z., Oglesby T.J., Atkinson J.P., Hack C.E., Becherer J.D. Dissection of CR1, factor H, membrane cofactor protein, and factor B binding and functional sites in the third complement component. J Immunol 1996 Jun 15; 156 (12): 4821–32.

80. Blom A.M., Webb J., Villoutreix B.O., Dahlbäck B. A Cluster of Positively Charged Amino Acids in the C4BP -Chain Is Crucial for C4b Binding and Factor I Cofactor Function. J Biol Chem 1999 Jul 2; 274 (27): 19237–45.

81. Blom A.M., Kask L., Dahlbäck B. Structural Requirements for the Complement Regulatory Activities of C4BP. J Biol Chem 2001 Jul 20; 276 (29): 27136–44.

82. Blom A.M., Villoutreix B.O., Dahlbäck B. Mutations in alpha-chain of C4BP that selectively affect its factor I cofactor function. J Biol Chem 2003 Oct 31; 278 (44): 43437–42.

83. Nicholson-Weller A., Wang C.E. Structure and function of decay accelerating factor CD55. J Lab Clin Med 1994 Apr; 123(4): 485–91.

84. Hourcade D.E., Mitchell L., Kuttner-Kondo L.A., Atkinson J.P., Medof M.E. Decay-accelerating Factor (DAF), Complement Receptor 1 (CR1), and Factor H Dissociate the Complement AP C3 Convertase (C3bBb) via Sites on the Type A Domain of Bb. J Biol Chem 2002 Jan 11; 277 (2): 1107–12.

85. Fujita T., Inoue T., Ogawa K., Iida K., Tamura N. The mechanism of action of decay-accelerating factor (DAF). DAF inhibits the assembly of C3 convertases by dissociating C2a and Bb. Journal of Experimental Medicine 1987 Nov 1; 166 (5): 1221–8.

86. Maciejewski J.P., Young N.S., Yu.M., Anderson S.M., Sloand E.M. Аnalysis of the expression of glycosylphosphatidylinositol anchored proteins on platelets from patients with paroxysmal nocturnal hemoglobinuria. Thrombosis Research 1996 Sep 15; 83 (6): 433–47.

87. Meri S., Morgan B.P., Davies A., Daniels R.H., Olavesen M.G., Waldmann H., et al. Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers. Immunol 1990 Sep; 71 (1): 1–9.

88. Morgan B.P. The membrane attack complex as an inflammatory trigger. Immunobiology 2016 Jun 1; 221 (6): 747–51.

89. Huang Y., Qiao F., Abagyan R., Hazard S., Tomlinson S. Defining the CD59-C9 binding interaction. J Biol Chem 2006 Sep 15; 281 (37): 27398–404.

90. Liszewski M.K., Post T.W., Atkinson J.P. Membrane Cofactor Protein (MCP or CD46): Newest Member of the Regulators of Complement Activation Gene Cluster. Annu Rev Immunol 1991; 9 (1): 431–55.

91. Barilla-LaBarca M.L., Liszewski M.K., Lambris J.D., Hourcade D., Atkinson J.P. Role of membrane cofactor protein (CD46) in regulation of C4b and C3b deposited on cells. J Immunol 2002 Jun 15; 168 (12): 6298–304.

92. Smith B.O., Mallin R.L., Krych-Goldberg M., Wang X., Hauhart R.E., Bromek K., et al. Structure of the C3b Binding Site of CR1 (CD35), the Immune Adherence Receptor. Cell 2002 Mar 22; 108 (6): 769–80.

93. Underhill D.M., Ozinsky A. Phagocytosis of microbes: complexity in action. Annu Rev Immunol 2002; 20: 825–52.

94. Zewde N., Jr R.D.G., Dorado A., Morikis D. Quantitative Modeling of the Alternative Pathway of the Complement System. PLOS ONE 2016 Mar 31; 11 (3): e0152337.

95. Pangburn M.K., Rawal N. Structure and function of complement C5 convertase enzymes. Biochemical Society Transactions 2002 Nov 1; 30 (6): 1006–10.

96. Dempsey P.W., Allison M.E., Akkaraju S., Goodnow C.C., Fearon D.T. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 1996 Jan 19; 271 (5247): 348–50.

97. Isaák A., Prechl J., Gergely J., Erdei A. The role of CR2 in autoimmunity. Autoimmunity 2006 Aug; 39 (5): 357–66.

98. Roozendaal R., Carroll M.C. Complement receptors CD21 and CD35 in humoral immunity. Immunol Rev 2007 Oct; 219: 157–66.

99. Vik D.P., Fearon D.T. Cellular distribution of complement receptor type 4 (CR4): expression on human platelets. J Immunol 1987 Jan 1; 138 (1): 254–8.

100. Cosgrove L.J., d’Apice A.J., Haddad A., Pedersen J., McKenzie I.F. CR3 receptor on platelets and its role in the prostaglandin metabolic pathway. Immunol Cell Biol 1987 Dec; 65 (Pt 6): 453–60.

101. He J.Q., Wiesmann C., van Lookeren Campagne M. A role of macrophage complement receptor CRIg in immune clearance and inflammation. Mol Immunol 2008 Oct; 45 (16): 4041–7.

102. Gorgani N.N., He J.Q., Katschke K.J., Helmy K.Y., Xi H., Steffek M., et al. Complement receptor of the Ig superfamily enhances complement-mediated phagocytosis in a subpopulation of tissue resident macrophages. J Immunol 2008 Dec 1; 181 (11): 7902–8.

103. Helmy K.Y., Katschke K.J., Gorgani N.N., Kljavin N.M., Elliott J.M., Diehl L., et al. CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens. Cell 2006 Mar 10; 124 (5): 915–27.

104. Wiesmann C., Katschke K.J., Yin J., Helmy K.Y., Steffek M., Fairbrother W.J., et al. Structure of C3b in complex with CRIg gives insights into regulation of complement activation. Nature 2006 Nov 9; 444 (7116): 217–20.

105. Fonseca M.I., Carpenter P.M., Park M., Palmarini G., Nelson E.L., Tenner A.J. C1qR(P), a myeloid cell receptor in blood, is predominantly expressed on endothelial cells in human tissue. J Leukoc Biol 2001 Nov; 70 (5): 793–800.

106. Arbesu I., Bucsaiova M., Fischer M.B., Mannhalter C. Platelet‐borne complement proteins and their role in platelet–bacteria interactions. J Thromb Haemost 2016 Nov; 14 (11): 2241–52.

107. Aksamit R.R., Falk W., Leonard E.J. Chemotaxis by mouse macrophage cell lines. J Immunol 1981 Jun; 126 (6): 2194–9.

108. Murakami Y., Imamichi T., Nagasawa S. Characterization of C3a anaphylatoxin receptor on guinea-pig macrophages. Immunology 1993 Aug; 79 (4): 633–8.

109. Elsner J., Oppermann M., Czech W., Dobos G., Schöpf E., Norgauer J., et al. C3a activates reactive oxygen radical species production and intracellular calcium transients in human eosinophils. Eur J Immunol 1994 Mar; 24 (3): 518–22.

110. Ehrengruber M.U., Geiser T., Deranleau D.A. Activation of human neutrophils by C3a and C5A. Comparison of the effects on shape changes, chemotaxis, secretion, and respiratory burst. FEBS Lett 1994 Jun 13; 346 (2–3): 181–4.

111. Elsner J., Oppermann M., Czech W., Kapp A. C3a activates the respiratory burst in human polymorphonuclear neutrophilic leukocytes via pertussis toxin-sensitive G-proteins. Blood 1994 Jun 1; 83 (11): 3324–31.

112. Kretzschmar T., Jeromin A., Gietz C., Bautsch W., Klos A., Köhl J., et al. Chronic myelogenous leukemia-derived basophilic granulocytes express a functional active receptor for the anaphylatoxin C3a. Eur J Immunol 1993 Feb; 23 (2): 558–61.

113. Lett-Brown M.A., Leonard E.J. Histamine-induced inhibition of normal human basophil chemotaxis to C5a. J Immunol 1977 Mar; 118 (3): 815–8.

114. el-Lati S.G., Dahinden C.A., Church M.K. Complement peptides C3a- and C5a-induced mediator release from dissociated human skin mast cells. J Invest Dermatol 1994 May; 102 (5): 803–6.

115. Nataf S., Davoust N., Ames R.S., Barnum S.R. Human T-cells express the C5a receptor and are chemoattracted to C5a. J Immunol 1999 Apr 1; 162 (7): 4018–23.

116. Zhao Y., Xu H., Yu W., Xie B.-D. Complement anaphylatoxin C4a inhibits C5a-induced neointima formation following arterial injury. Mol Med Rep 2014 Jul; 10 (1): 45–52.

117. Tsuruta T., Yamamoto T., Matsubara S., Nagasawa S., Tanase S., Tanaka J., et al. Novel function of C4a anaphylatoxin. Release from monocytes of protein which inhibits monocyte chemotaxis. Am J Pathol 1993 Jun; 142 (6): 1848–57.

118. Coulthard L.G., Woodruff T.M. Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence and the myth. J Immunol 2015 Apr 15; 194 (8): 3542–8.

119. Matthews K.W., Mueller-Ortiz S.L., Wetsel R.A. Carboxypeptidase N: a pleiotropic regulator of inflammation. Mol Immunol 2004 Jan;40 (11): 785–93.

120. Mueller-Ortiz S.L., Wang D., Morales J.E., Li L., Chang J.-Y., Wetsel R.A. Targeted disruption of the gene encoding the murine small subunit of carboxypeptidase N (CPN1) causes susceptibility to C5a anaphylatoxin-mediated shock. J Immunol 2009 May 15; 182 (10): 6533–9.

121. Bajic G., Yatime L., Klos A., Andersen G.R. Human C3a and C3a desArg anaphylatoxins have conserved structures, in contrast to C5a and C5a desArg. Protein Sci 2013 Feb; 22 (2): 204–12.

122. Sayah S., Jauneau A.C., Patte C., Tonon M.C., Vaudry H., Fontaine M. Two different transduction pathways are activated by C3a and C5a anaphylatoxins on astrocytes. Brain Res Mol Brain Res 2003 Apr 10; 112 (1–2): 53–60.

123. Flierman R., Daha M.R. The clearance of apoptotic cells by complement. Immunobiology 2007; 212 (4–5): 363–70.

124. Trouw L.A., Blom A.M., Gasque P. Role of complement and complement regulators in the removal of apoptotic cells. Mol Immunol 2008 Mar 1; 45 (5): 1199–207.

125. Kemper C., Mitchell L.M., Zhang L., Hourcade D.E. The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis. PNAS USA 2008 Jul 1; 105 (26): 9023–8.

126. Taylor P.R., Carugati A., Fadok V.A., Cook H.T., Andrews M., Carroll M.C., et al. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med 2000 Aug 7; 192 (3): 359–66.

127. Nauta A.J., Daha M.R., van Kooten C., Roos A. Recognition and clearance of apoptotic cells: a role for complement and pentraxins. Trends in Immunology 2003 Mar 1; 24(3): 148–54.

128. Gershov D., Kim S., Brot N., Elkon K.B. C-Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 2000 Nov 6; 192 (9): 1353–64.

129. Mihlan M., Stippa S., Józsi M., Zipfel P.F. Monomeric CRP contributes to complement control in fluid phase and on cellular surfaces and increases phagocytosis by recruiting factor H. Cell Death Differ 2009 Dec; 16 (12): 1630–40.

130. Cook H.T., Botto M. Mechanisms of Disease: the complement system and the pathogenesis of systemic lupus erythematosus. Nat Clin Pract Rheumatol 2006 Jun; 2 (6): 330–7.

131. Carroll M.C. A protective role for innate immunity in systemic lupus erythematosus. Nat Rev Immunol 2004 Oct; 4 (10): 825–31.

132. Botto M., Kirschfink M., Macor P., Pickering M.C., Würzner R., Tedesco F. Complement in human diseases: Lessons from complement deficiencies. Mol Immunol 2009 Sep; 46 (14): 2774–83.


Для цитирования:


Шахиджанов С.С., Филиппова А.Е., Бутылин А.А., Атауллаханов Ф.И. Cовременное представление о системе комплемента. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2019;18(3):130-144. https://doi.org/10.24287/1726-1708-2019-18-3-130-144

For citation:


Shakhidzhanov S.S., Filippova A.E., Butilin A.A., Ataullakhanov F.I. A modern view on the complement system. Pediatric Hematology/Oncology and Immunopathology. 2019;18(3):130-144. (In Russ.) https://doi.org/10.24287/1726-1708-2019-18-3-130-144

Просмотров: 66


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 1726-1708 (Print)
ISSN 2414-9314 (Online)