Antimicrobial proteins and peptides of neutrophilic granulocytes as modulators of complement system

Abstract

Neutrophilic granulocytes (neutrophils) and complement system are important factors of the innate immunity of vertebrates. Due to a long coevolution different interactions between them have been established. The data about action of antimicrobial proteins and peptides of neutrophils on complement have been collected to date. In this paper, the biology of neutrophils and complement is briefly considered and research reports are reviewed to systematize data about action of myeloperoxidase, reactive oxygen species, lysozyme, antimicrobial peptides, lactoferrin, neutrophilic extracellular traps, neutrophil fragments and total matter on human complement. Physiological and pathophysiological role of this modulation is emphasized.

Keywords:complement system; neutrophils; antimicrobial proteins; antimicrobial peptides; inflammation; review

For citation: Krenev I.A., Berlov M.N., Umnyakova E.S. Antimicrobial proteins and peptides of neutrophilic granulocytes as modulators of complement system. Immunologiya. 2021; 42 (4): 426-33. DOI: https://doi.org/10.33029/0206-4952-2021-42-4-426-433 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

References

1. Hartenstein V. Blood cells and blood cell development in the animal kingdom. Annu. Rev. Cell Dev. Biol. 2006; 22: 677–712. DOI: https://doi.org/10.1146/annurev.cellbio.22.010605.093317

2. Nonaka M. Evolution of the complement system. In: Anderluh G., Gilbert R. (eds). MACPF/CDC Proteins – Agents of Defence, Attack and Invasion. Dordrecht: Springer, 2014: 31–43. DOI: https://doi.org/10.1007/978-94-017-8881-6_3

3. Botto M., Lissandrini D., Sorio C., Walport M.J. Biosynthesis and secretion of complement component (C3) by activated human polymorphonuclear leukocytes. J. Immunol. 1992; 149 (4): 1348–55. PMID: 1500721.

4. Wirthmueller U., Dewald B., Thelen M., Schäfer M.K., Stover C., Whaley K., North J., Eggleton P., Reid K.B., Schwaeble W.J. Properdin, a positive regulator of complement activation, is released from secondary granules of stimulated peripheral blood neutrophils. J. Immunol. 1997; 158 (9): 4444–51. PMID: 9127010.

5. Goldstein I.M., Weismann G. Generation of C5-derived lysosomal enzyme-releasing activity (C5a) by lysates of leucocyte lysosomes. J. Immunol. 1974; 113 (5): 1583–8. PMID: 4473046.

6. Johnson U., Ohlsson K., Olsson I. Effects of granulocyte neutral proteases on complement components. Scand. J. Immunol. 1976; 5 (4): 421–6. DOI: https://doi.org/10.1111/j.1365-3083.1976.tb00296.x

7. Orr F.W., Varani J., Kreutzer D.L., Senior R.M., Ward P.A. Digestion of the fifth component of complement by leukocyte enzymes. Sequential generation of chemotactic activities for leukocytes and for tumor cells. Am. J. Pathol. 1979; 94 (1): 75–83. PMID: 569981.

8. Taylor J.C., Crawford I.P., Hugli T.E. Limited degradation of the third component (C3) of human complement by human leukocyte elastase (HLE): partial characterization of C3 fragments. Biochemistry. 1977; 16 (15): 3390–6.

9. Venge P., Olsson I. Cationic proteins of human granulocytes. VI. Effects on the complement system and mediation of chemotactic activity. J. Immunol. 1975; 115 (6): 1505–08.

10. Vogt W. Cleavage of the fifth component of complement and generation of a functionally active C5b6-like complex by human leukocyte elastase. Immunobiology. 2000; 201 (3–4): 470–7. DOI: https://doi.org/10.1016/S0171-2985(00)80099-6

11. Ward P.A., Hill J.H. C5 chemotactic fragments produced by an enzyme in lysosomal granules of neutrophils. J. Immunol. 1970; 104 (3): 535–43. PMID: 4985169.

12. Lajoie S., Wills-Karp M. New twist in an ancient immune pathway. Immunity. 2013; 39 (6): 1000–2. DOI: https://doi.org/10.1016/j.immuni.2013.11.015

13. Берлов М.Н., Умнякова Е.С., Кокряков В.Н. Белки и пептиды нейтрофилов в регуляции системы комплемента. Патогенез. 2017; 15 (1): 19–23. DOI: https://doi.org/10.25557/GM.2017.1.6947 [Berlov M.N., Umnyakova E.S., Kokryakov V.N. Proteins and peptides of neutrophils in regulation of complement system. Pathogenesis. 2017; 15 (1): 19–23. DOI: https://doi.org/10.25557/GM.2017.1.6947 (in Russian)]

14. Futosi K., Fodor S., Mócsai A. Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int. Immunopharmacol. 2013; 17 (3): 638–50. DOI: https://doi.org/10.1016/j.intimp.2013.06.034

15. Paoliello-Paschoalato A.B., Marchi L.F., de Andrade M.F., Kabeya L.M., Donadi E.A., Lucisano-Valim Y.M. Fcγ and complement receptors and complement proteins in neutrophil activation in rheumatoid arthritis: contribution to pathogenesis and progression and modulation by natural products. Evid. Based Complement. Alternat. Med. 2015; 2015: 429878. DOI: https://doi.org/10.1155/2015/429878

16. Cassatella M.A., Östberg N.K., Tamassia N., Soehnlein O. Biological roles of neutrophil-derived granule proteins and cytokines. Trends Immunol. 2019; 40 (7): 648–64. DOI: https://doi.org/10.1016/j.it.2019.05.003

17. Mantovani A., Cassatella M.A., Costantini C., Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat. Rev. Immunol. 2011; 11 (8): 519–31. DOI: https://doi.org/10.1038/nri3024

18. Thomas C.J., Schroder K. Pattern recognition receptor function in neutrophils. Trends Immunol. 2013; 34 (7): 317–28. DOI: https://doi.org/10.1016/j.it.2013.02.008

19. Brinkmann V., Reichard U., Goosmann C., Fauler B., Uhlemann Y., Weiss D.S., Weinrauch Y., Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science. 2004; 303 (5663): 1532–5. DOI: https://doi.org/10.1126/science.1092385

20. O’Donoghue A.J., Jin Y., Knudsen G. M., Perera N.C., Jenne D.E., Murphy J.E., Craik C.S., Hermiston T.W. Global substrate profiling of proteases in human neutrophil extracellular traps reveals consensus motif predominantly contributed by elastase. PLoS One. 2013; 8 (9): e75141. DOI: https://doi.org/10.1371/journal.pone.0075141

21. Nauseef W.M., Borregaard N. Neutrophils at work. Nat. Immunol. 2014; 15 (7): 602–11. DOI: https://doi.org/10.1038/ni.2921

22. Lachmann P.J. Looking back on the alternative complement pathway. Immunobiology. 2018; 223 (8–9): 519–23. DOI: https://doi.org/10.1016/j.imbio.2018.02.001

23. Pillemer L., Blum L., Lepow I.H., Ross O.A., Todd E.W., Wardlaw A.C. The properdin system and immunity. I. Demonstration and isolation of a new serum protein, properdin, and its role in immune phenomena. Science. 1954; 120 (3112): 279–85. DOI: https://doi.org/10.1126/science.120.3112.279

24. Ricklin D., Reis E.S., Mastellos D.C., Gros P., Lambris J.D. Complement component C3 – the «Swiss Army Knife» of innate immunity and host defense. Immunol. Rev. 2016; 274 (1): 33–58. DOI: https://doi.org/10.1111/imr.12500

25. Morgan B.P., Boyd C., Bubeck D. Molecular cell biology of complement membrane attack. Semin. Cell Dev. Biol. 2017; 72: 124–32. DOI: https://doi.org/10.1016/j.semcdb.2017.06.009

26. Klos A., Wende E., Wareham K.J., Monk P.N. International Union of Basic and Clinical Pharmacology. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol. Rev. 2013; 65 (1): 500–43. DOI: https://doi.org/10.1124/pr.111.005223

27. Huber-Lang M., Ekdahl K.N., Wiegner R., Fromell K., Nilsson B. Auxiliary activation of the complement system and its importance for the pathophysiology of clinical conditions. Semin. Immunopathol. 2018; 40 (1): 87–102. DOI: https://doi.org/10.1007/s00281-017-0646-9

28. Aratani Y. Myeloperoxidase: its role for host defense, inflammation, and neutrophil function. Arch. Biochem. Biophys. 2018; 640: 47–52. DOI: https://doi.org/10.1016/j.abb.2018.01.004

29. Vogt W., Damerau B., von Zabern I., Nolte R., Brunahl D. Non-enzymic activation of the fifth component of human complement, by oxygen radicals. Some properties of the activation product, C5b-like C5. Mol. Immunol. 1989; 26 (12): 1133–42. DOI: https://doi.org/10.1016/0161-5890(89)90057-6

30. Vogt W., Zimmermann B., Hesse D., Nolte R. Activation of the fifth component of human complement, C5, without cleavage, by methionine oxidizing agents. Mol. Immunol. 1992; 29 (2): 251–6. DOI: https://doi.org/10.1016/0161-5890(92)90106-8

31. Vogt W. Complement activation by myeloperoxidase products released from stimulated human polymorphonuclear leukocytes. Immunobiology. 1996; 195 (3): 334–46. DOI: https://doi.org/10.1016/S0171-2985(96)80050-7

32. Vogt W., Hesse D. Oxidants generated by the myeloperoxidase-halide system activate the fifth component of human complement, C5. Immunobiology. 1994; 192 (1–2): 1–9. DOI: https://doi.org/10.1016/S0171-2985(11)80403-1

33. Shingu M., Nonaka S., Nishimukai H., Nobunaga M., Kitamura H., Tomo-Oka K. Activation of complement in normal serum by hydrogen peroxide and hydrogen peroxide-related oxygen radicals produced by activated neutrophils. Clin. Exp. Immunol. 1992; 90 (1): 72–8. DOI: https://doi.org/10.1111/j.1365-2249.1992.tb05834.x

34. Clark R.A., Szot S., Venkatasubramanian K., Schiffmann E. Chemotactic factor inactivation by myeloperoxidase-mediated oxidation of methionine. J. Immunol. 1980; 124 (4): 2020–6. PMID: 6245132.

35. Coble B.I., Dahlgren C., Hed J., Stendahl O. Myeloperoxidase reduces the opsonizing activity of immunoglobulin G and complement component C3b. Biochim. Biophys. Acta. 1984; 802 (3): 501–5. DOI: 10.1016/0304-4165(84)90369-6.

36. O’Flynn J., Dixon K.O., Faber Krol M.C., Daha M.R., van Kooten C. Myeloperoxidase directs properdin-mediated complement activation. J. Innate Immun. 2014; 6 (4): 417–25. DOI: https://doi.org/10.1159/000356980

37. Harboe M., Johnson C., Nymo S., Ekholt K., Schjalm C., Lindstad J.K., Pharo A., Hellerud B.C., Nilsson Ekdahl K., Mollnes T.E., Nilsson P.H. Properdin binding to complement activating surfaces depends on initial C3b deposition. Proc. Natl Acad. Sci. USA. 2017; 114 (14): E534–9. DOI: https://doi.org/10.1073/pnas.1612385114

38. Zabucchi G., Menegazzi R., Roncelli L., Bertoncin P., Tedesco F., Patriarca P. Protective and inactivating effects of neutrophil myeloperoxidase on C1q activity. Inflammation. 1990. 14 (1): 41–53. DOI: https://doi.org/10.1007/BF00914028

39. Pellegrini A., Thomas U., von Fellenberg R., Wild P. Bactericidal activities of lysozyme and aprotinin against gram-negative and gram-positive bacteria related to their basic character. J. Appl. Bacteriol. 1992; 72 (3): 180–7. DOI: https://doi.org/10.1111/j.1365-2672.1992.tb01821.x

40. Callewaert L., Michiels C.W. Lysozymes in the animal kingdom. J. Biosci. 2010; 35 (1): 127–60. DOI: https://doi.org/10.1007/s12038-010-0015-5

41. Ragland S.A., Criss A.K. From bacterial killing to immune modulation: Recent insights into the functions of lysozyme. PLoS Pathog. 2017; 13 (9): e1006512. DOI: https://doi.org/10.1371/journal.ppat.1006512

42. Glynn A.A. The complement lysozyme sequence in immune bacteriolysis. Immunology. 1969; 16 (4): 463–71. PMID: 4890313.

43. Martinez R.J., Carroll S.F. Sequential metabolic expressions of the lethal process in human serum-treated Escherichia coli: role of lysozyme. Infect. Immun. 1980; 28 (3): 735–45. PMID: 6156906.

44. Bloch E.F., McDonald-Pinkett S., Campbell S., Baskin S., Dillahunt S., Peters S., Lucas S., Evans D., Johnson C., Everett T., Kanaan Y. New mechanism for complement killing of Gram-negative bacteria. Afr. J. Microbiol. Res. 2011; 5 (23): 3936–41. DOI: https://doi.org/10.5897/AJMR

45. Ogundele M.O. A novel anti-inflammatory activity of lysozyme: modulation of serum complement activation. Mediators Inflamm. 1998; 7 (5): 363–5. DOI: https://doi.org/10.1080/09629359890893

46. Kozlov L.V., Lakhtin V.M., Batalova T.N., Gouzova V.A., D’yakov V.L., Romanov S.V. Inhibition by an egg lysozyme of three stages of an enzymatic cascade of activation of a classic path of a human complement. Vestnik Moskovskogo Universiteta. Seriya 2. Khimiya. 2000; 41 (6): 88–90.

47. Panyutich A.V., Szold O., Poon P.H., Tseng Y., Ganz T. Identification of defensin binding to C1 complement. FEBS Lett. 1994; 356 (2–3): 169–73. DOI: https://doi.org/10.1016/0014-5793(94)01261-x

48. Panyutich A.V., Hiemstra P.S., van Wetering S., Ganz T. Human neutrophil defensin and serpins form complexes and inactivate each other. Am. J. Respir. Cell Mol. Biol. 1995; 12 (3): 351–7. DOI: https://doi.org/10.1165/ajrcmb.12.3.7873202

49. Prohászka Z., Német K., Csermely P., Hudecz F., Mezõ G., Füst G. Defensins purified from human granulocytes bind C1q and activate the classical complement pathway like the transmembrane glycoprotein gp41 of HIV-1. Mol. Immunol. 1997; 34 (11): 809–16. DOI: https://doi.org/10.1016/s0161-5890(97)00097-7

50. van den Berg R.H., Faber-Krol M.C., van Wetering S., Hiemstra P.S., Daha M.R. Inhibition of activation of the classical pathway of complement by human neutrophil defensins. Blood. 1998; 92 (10): 3898–903. DOI: https://doi.org/10.1182/blood.V92.10.3898

51. Groeneveld T.W., Ramwadhdoebé T.H., Trouw L.A., van den Ham D.L., van der Borden V., Drijfhout J.W., Hiemstra P.S., Daha M.R., Roos A. Human neutrophil peptide-1 inhibits both the classical and the lectin pathway of complement activation. Mol. Immunol. 2007; 44 (14): 3608–14. DOI: https://doi.org/10.1016/j.molimm.2007.03.003

52. Берлов М.Н., Умнякова Е.С., Леонова Т.С., Пашинская Л.Д., Кокряков В.Н. Действие антимикробных пептидов на активацию системы комплемента. Российский иммунологический журнал. 2016; 10 (19): 75–7. [Berlov M.N., Umnyakova E.S., Leonova T.S., Pashinskaya L.D., Kokryakov V.N. Action of antimicrobial peptides on activation of complement system. Russian Journal of Immunology. 2016; 10 (19): 75–7. (in Russian)]

53. González-Chávez S.A., Arévalo-Gallegos S., Rascón-Cruz Q. Lactoferrin: structure, function and applications. Int. J. Antimicrob. Agents. 2009; 33 (4): 301.e1–8. DOI: https://doi.org/10.1016/j.ijantimicag.2008.07.020

54. Tomita M., Bellamy W., Takase M., Yamauchi K., Wakabayashi H., Kawase K. Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin. J. Dairy Sci. 1991; 74 (12): 4137–42. DOI: https://doi.org/10.3168/jds.S0022-0302(91)78608-6

55. Bellamy W., Takase M., Yamauchi K., Wakabayashi H., Kawase K., Tomita M. Identification of the bactericidal domain of lactoferrin. Biochim. Biophys. Acta. 1992; 1121 (1–2): 130–6. DOI: https://doi.org/10.1016/0167-4838(92)90346-f

56. Morgan O.S., Bankay J., Quash G.A. The effect of lactoferrin, an iron-binding protein on complement activity. West Indian Med. J. 1975; 24 (1): 46–54. PMID: 1169861.

57. Veerhuis R., Kijlstra A. Inhibition of hemolytic complement activity by lactoferrin in tears. Exp. Eye Res. 1982; 34 (2): 257–65. DOI: https://doi.org/10.1016/0014-4835(82)90059-8

58. Kievits F, Kijlstra A. Inhibition of C3 deposition on solid-phase bound immune complexes by lactoferrin. Immunology. 1985; 54 (3): 449–56. PMID: 3844370.

59. Kijlstra A., Jeurissen S.H. Modulation of classical C3 convertase of complement by tear lactoferrin. Immunology. 1982; 47 (2): 263–70. PMID: 6922088.

60. Samuelsen Ø., Haukland H.H., Ulvatne H., Vorland L.H. Anti-complement effects of lactoferrin-derived peptides. FEMS Immunol. Med. Microbiol. 2004; 41 (2): 141–8. DOI: https://doi.org/10.1016/j.femsim.2004.02.006

61. Rainard P. Activation of the classical pathway of complement by binding of bovine lactoferrin to unencapsulated Streptococcus agalactiae. Immunology. 1993; 79 (4): 648–52. PMID: 8406591.

62. Kaplan M.J., Radic M. Neutrophil extracellular traps: double-edged swords of innate immunity. J. Immunol. 2012; 189 (6): 2689–95. DOI: https://doi.org/10.4049/jimmunol.1201719

63. Leffler J., Martin M., Gullstrand B., Tydén H., Lood C., Truedsson L., Bengtsson A.A., Blom A.M. Neutrophil extracellular traps that are not degraded in systemic lupus erythematosus activate complement exacerbating the disease. J. Immunol. 2012; 188 (7): 3522–31. DOI: https://doi.org/10.4049/jimmunol.1102404

64. Wang H., Wang C., Zhao M.H., Chen M. Neutrophil extracellular traps can activate alternative complement pathways. Clin. Exp. Immunol. 2015; 181 (3): 518–27. DOI: https://doi.org/10.1111/cei.12654

65. Yuen J., Pluthero F.G., Douda D.N., Riedl M., Cherry A., Ulanova M., Kahr W.H., Palaniyar N., Licht C. NETosing neutrophils activate complement both on their own NETs and bacteria via alternative and non-alternative pathways. Front. Immunol. 2016; 7: 137. DOI: https://doi.org/10.3389/fimmu.2016.00137

66. Baker P.J., Lint T.F., Siegel J., Kies M.W., Gewurz H. Potentiation of C56-initiated lysis by leucocyte cationic proteins, myelin basic proteins and lysine-rich histones. Immunology. 1976; 30 (4): 467–73. PMID: 818007.

67. Asberg A.E., Mollnes T.E., Videm V. Complement activation by neutrophil granulocytes. Scand. J. Immunol. 2008; 67 (4): 354–61. DOI: https://doi.org/10.1111/j.1365-3083.2008.02077.x

68. Camous L., Roumenina L., Bigot S., Brachemi S., Frémeaux-Bacchi V., Lesavre P., Halbwachs-Mecarelli L. Complement alternative pathway acts as a positive feedback amplification of neutrophil activation. Blood. 2011; 117 (4): 1340–9. DOI: https://doi.org/10.1182/blood-2010-05-283564

69. Ohlsson S., Holm L., Hansson C., Ohlsson S. M., Gunnarsson L., Pettersson A., Skattum L. Neutrophils from ANCA-associated vasculitis patients show an increased capacity to activate the complement system via the alternative pathway after ANCA stimulation. PLoS One. 2019; 14 (6): e0218272. DOI: https://doi.org/10.1371/journal.pone.0218272

70. Xiao H., Schreiber A., Heeringa P., Falk R.J., Jennette J.C. Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies. Am. J. Pathol. 2007; 170 (1): 52–64. DOI: https://doi.org/10.2353/ajpath.2007.0

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