MorphologyMorphologyМорфология1026-35432949-2556Eco-Vector39952310.17816/morph.399523ArticlesСтатьиDISCOVERY OF THE NEUTROPHIL EXTRACELLULAR TRAPS BEGINS A NEW STAGE IN THE STUDY OF NEUTROPHIL MORPHOGENESIS AND FUNCTIONОТКРЫТИЕ НЕЙТРОФИЛЬНЫХ ВНЕКЛЕТОЧНЫХ ЛОВУШЕК - НОВЫЙ ЭТАП В ИЗУЧЕНИИ МОРФОГЕНЕЗА И ФУНКЦИЙ НЕЙТРОФИЛОВPerovaM DПероваМ Д

Краснодарский Центр пародонтологии и дентальной имплантации (руков. - проф. М.Д. Перова); Кубанский государственный медицинский университет

kav@mail.kuban.ruShubichM GШубичМ Г

Краснодарский Центр пародонтологии и дентальной имплантации (руков. - проф. М.Д. Перова); Кубанский государственный медицинский университет

kav@mail.kuban.ruPerovaM DShubichM GКубанский государственный медицинский университет150920111393NO3 (2011)№3 (2011)899609052023Copyright ©; 2011, Eco-VectorCopyright ©; 2011, Эко-Вектор2011Eco-VectorЭко-Векторhttps://j-morphology.com/1026-3543/article/view/399523

The purpose of the present review was to analyze the accumulating evidence regarding recently discovered novel defense mechanism of neutrophils - capacity to form neutrophil extracellular traps (NETs). Contact with pathogenic microbes and/or exposure to proinflammatory cytokines trigger the respiratory burst in the neutrophils with a subsequent initiation of a cell death (NETosis) which differs from apoptosis and necrosis. NETs are formed by the fibrils of decondensed chromatin (DNA/ histones), released from the neutrophil, which is closely associated with the antimicrobial proteins of cytoplasmic granules. Due to its three-dimensional structure, NETs are capable of retaining the microorganisms (bacteria, fungi and protozoa), while high local concentration of the antimicrobial substances provides their killing. The review presents the evidence of a potential defensive role of NETs in infectious diseases, traumas and surgical operations, as well as during the early stage of a repair process. Considering the role played by neutrophils in the immune response orientation via pentraxin-3 (PTX3), including the switching to adaptive immunity, it is necessary to study the subsequent interaction of DNA/histone exrtacellular structures with the tissue microenvironment.

Цель настоящего обзора - дать анализ накопленным фактам о недавно открытом новом защитном свойстве нейтрофилов - способности образовывать внеклеточные нейтрофильные ловушки - NETs. Контакт с патогенными микробами и/или воздействие провоспалительных цитокинов запускает в нейтрофилах респираторный взрыв с последующей инициацией клеточной гибели (нэтоз), которая отличается от апоптоза и некроза. NETs образованы выброшенными из нейтрофила фибриллами деконденсированного хроматина (ДНК/гистоны), который тесно ассоциирован с антимикробными белками цитоплазматических гранул. Благодаря своей трёхмерной структуре NETs способны фиксировать микроорганизмы (бактерии, грибы, простейшие), а высокая локальная концентрация антимикробных веществ обеспечивает их уничтожение. В обзоре приведены сведения о защитной роли NETs при инфекционных заболеваниях, травмах и хирургических вмешательствах, а также в ранней фазе репаративного процесса. Принимая во внимание, что нейтрофилы участвуют в ориентации иммунного ответа посредством пентраксина-3 (PTX3), в том числе в переключении на адаптивный иммунный ответ, необходимо изучение последующих взаимодействий внеклеточных ДНК-гистоновых структур с тканевым микроокружением.

neutrophil granulocytesextracellular neutrophil traps (NETs)нейтрофильные гранулоцитывнеклеточные нейтрофильные ловушки (NETs)Авдеева М.Г., Лебедев В.В. и Шубич М.Г. Новые молекулярные механизмы развития инфекционного процесса. Клин. лаб. диагностика, 2007, № 4, с. 12-22.Авдеева М.Г. и Шубич М.Г. Патогенетические механизмы инициации синдрома системного воспалительного ответа (обзор литературы). Клин. лаб. диагностика, 2003, № 6, с. 3-9.Безредка А.М. История одной идеи. Творчество Мечникова. Харьков, Научная мысль, 1926.Быков В.Л. Цитология и общая гистология (функциональная морфология клеток и тканей человека). СПб., СОТИС, 2001.Коротяев А.И. и Бабичев С.А. Медицинская микробиология, иммунология и вирусология. 4-е изд. СПб., СпецЛит, 2008.Маянский А.Н. и Маянский Д.Н. Очерки о нейтрофиле и макрофаге. Новосибирск, Наука, 1983.Мечников И.И. Лекции о сравнительной патологии воспаления. М., Гос. изд-во мед. лит-ры, 1947.Мечников И.И. Исследования о внутриклеточном пищеварении у беспозвоночных. В кн.: Акад. собр. соч., т. 6. М., Изд-во АН СССР, 1952, с. 3-21.Мечников И.И. О целебных свойствах организма. Там же, с. 22-29.Мечников И.И. Об отношении фагоцитов к бациллам сибирской язвы. Там же, с. 41-59.Мечников И.И. О борьбе клеток против рожистого стрептококка. Там же, с. 63- 90.Перова М.Д. и Шубич М.Г. Молекулярные аспекты инициации и развития воспалительно-деструктивных заболеваний пародонта. Арх. пат., 2006, т. 68, № 5, с. 59-63.Перова М.Д., Шубич М.Г., Козлов В.А. и Тропина А.В. Результаты аутотрансплантации васкулярно-стромальноклеточной фракции при пародонтите и особенности формирования тканевого регенерата. Институт стоматологии, 2010, т. 42, № 2, с. 62- 64.Шубич М.Г. и Тивкова И.В. Фагоцитарная революция в медицине (к 100-летию присуждения И.И. Мечникову Нобелевской премии, 1908 г.). Морфология, 2009, т.135, вып. 1, с. 70- 75.Alghamdi A.S. and Foster D.N. Seminal DNase frees spermatozoa entangled in neutrophil extracellular traps. Biol. Reprod., 2005, v. 73, p. 1174-1181.Alles V., Bottazzi B., Peri G. et al. Inducible expression of PTX3, a new member of the pentraxin family, in human mononuclear phagocytes. Blood, 1994, v. 84, p. 3483-3493.Baker V.S., Imade G.E., Molta N.B. et al. Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in plasmodium falciparum infected children under six years of age. Malar. J., 2008, v. 7, p. 41-46.Beiter K., Wartha F., Albiger B. et al. An endonuclease allows Streptococcus pneumoniae to escape from neutrophil extracellular traps. Curr. Biol., 2006, v. 16, p. 401-407.Borregaard N. and Cowland J.B. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood, 1997, v. 89, p. 3503-3521.Bottazzi B., Doni A., Garlanda C. and Mantovani A. An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu. Rev. Immunol., 2010, v. 8, p. 157-183.Bottazzi B., Garlanda C., Cotena A. et al. The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: interplay with cellular innate immunity. Immunol. Rev., 2009, v. 227, p. 9-18.Brinkmann V., Reichard U., Goosmann C. et al. Neutrophil extracellular traps kill bacteria. Science, 2004, v. 303, p. 1532-1535.Brinkmann V. and Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat. Rev. Microbiol., 2007, v. 5, p. 577-582.Buchanan J.T., Simpson A.J., Aziz R.K. et al. DNase expression allows the pathogen group A Streptococcus to escape killing in neutrophil extracellular traps. Curr. Biol., 2006, v. 16, p. 396-400.Clark S.R., Ma A.C., Tavener S.A. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat. Med., 2007, v. 13, p. 463-469.Doni A., Peri G., Chieppa M. et al. Production of the soluble pattern recognition receptor PTX3 by myeloid, but not plasmacytoid, dendritic cells. Eur. J. Immunol., 2003, v. 33, p. 2886-2893.Elsbach P., Weiss J. and Levy O. Integration of antimicrobial host defenses: role of the bactericidal/permeability-increasing protein. Trends. Microbiol., 1994, v. 2, p. 324-328.Ermert D., Urban C.F., Laube B. et al. Mouse neutrophil extracellular traps in microbial infections. J. Innate Immun., 2009, v. 1, p. 181-193.Fadeel B., Ahlin A., Henter J. et al. Involvement of caspases in neutrophil apoptosis: regulation by reactive oxygen species. Blood, 1998, v. 92, p. 4808-4818.Fairhurst A.M., Wandstrat A.E. and Wakeland E.K. Systemic lupus erythematosus: multiple immunological phenotypes in a complex genetic disease. Adv. Immunol., 2006, v. 92, p. 59-69.Fuchs T.A., Abed U., Goosmann C. et al. Novel cell death program leads to neutrophil extracellular traps. J. Cell Biol., 2007, v. 176, p. 231-241.Garlanda C., Hirsch E., Bozza S. et al. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature, 2002, v. 420, p. 182-186.Guimaraes-Costa A.B., Nascimento M.T., Froment G.S. et al. Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps. Proc. Natl. Acad. Sci. USA, 2009, v. 106, p. 6748-6753.Gupta A.K., Hasler P., Holzgreve W. et al. Induction of neutrophil extracellular DNA lattices by placental microparticles and IL-8 and their presence in preeclampsia. Hum. Immunol., 2005, v. 66, p. 1146-1154.Hampton M., Kettle A. and Winterbourn C. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood, 1998, v. 92, p. 3007-3017.Henson P.E., Henson J.E., Fittschen C. et al. Degranulation and secretion by phagocytic cell. In: Inflammation: Basic Principles and Clinical Correlates. 2nd ed. N.Y., Raven Press, 1992, p. 511-539.Hong W., Juneau R.A., Pang B. and Swords W.E. Survival of bacterial biofilms within neutrophil extracellular traps promotes nontypeable Haemophilus influenzae persistence in the chinchilla model for otitis media. J. Innate Immun., 2009, v. 1, p. 215-224.Inforzato A., Peri G., Doni A. et al. Structure and function of the long pentraxin PTX3 glycosidic moiety: fine-tuning of the interaction with C1q and complement activation. Biochemistry, 2009, v. 45, p. 11540-11551.Jaillon S., Peri G., Delneste Y. et al. The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps. J. Exp. Med., 2007, v. 204, p. 793-804.Jeannin P., Bottazzi B., Sironi M. et al. Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors. Immunity, 2005, v. 22, p. 551-560.Kessenbrock K., Krumbholz M., Schönermarck U. et al. Netting neutrophils in autoimmune small-vessel vasculitis. J. Am. Soc. Nephrol., 2009, v. 15, p. 623-625.Klebanoff S.J. Oxygen metabolites from phagocytes. In Inflammation: Basic Principles and Clinical Correlates. 3nd ed. Philadelphia, Lippincott Williams & Wilkins, 1999, p. 721-768.Koenig J.M. and Yoder M.C. Neonatal neutrophils: the good, the bad, and the ugly. Clin. Perinatol., 2004, v. 31, p. 39-51.Köckritz-Blickwede M. von and Nizet V. Innate immunity turned inside-out: antimicrobial defense by phagocyte extracellular traps. J. Mol. Med., 2009, v. 87, p. 775-783.Lambeth J.D. Nox enzymes and the biology of reactive oxygen. Nat. Rev., 2004, v. 4, p. 181-189.Lippolis J.D., Reinhardt T.A., Goff J.P. and Horst R.L. Neutrophil extracellular trap formation by bovine neutrophils is not inhibited by milk. Vet. Immunol. Immunopathol., 2006, v.113, p.248-255.Lominadze G., Powell D.W., Luerman G.C. et al. Proteomic analysis of human neutrophil granules. Mol. Cell. Proteomics, 2005, v. 4, p. 1503-1521.Mantovani A., Garlanda C., Doni A and Bottazzi B. Pentraxins in innate immunity: from C-reactive protein to the long pentraxin PTX3. J. Clin. Immunol., 2008, v. 28, p. 1-13.Margraf S., Logters T., Reipen J. et al. Neutrophil-derived circulating free DNA (cf-DNA/NETs): a potential prognostic marker for posttraumatic development of inflammatory second hit and sepsis. Shock, 2008, v. 30, p. 352-358.Martinelli S., Urosevic M., Daryadel A. et al. Induction of genes mediating interferon-dependent extracellular trap formation during neutrophil differentiation. J. Biol. Chem., 2004, v. 279, p. 44123-44132.Medzhitov R., Preston-Hurlburt P. and Janeway C.A. Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature, 1997, v. 388, p. 394-405.Munafo D.B., Johnson J.L., Brzezinska A.A. et al. DNase I inhibits a late phase of reactive oxygen species production in neutrophils. J. Innate Immun., 2009, v. 6, p. 527-542.Murphy K., Travers P. and Walport M. Janeway's Immunobiology. 7th ed., N.Y., Garland Science, 2008.Nathan C. Neutrophils and immunity: challenges and opportunities. Nat. Rev. Immunol., 2006, v. 6, p. 173-182.Nauta A.J., Daha M.R., van Kooten C. and Roos A. Recognition and clearance of apoptotic cells: a role for complement and pentraxins. Trends Immunol., 2003, v. 24, p. 148-154.Nimmerjahn F. and Ravetch J.V. Anti-inflammatory actions of intravenous immunoglobulin. Annu. Rev. Immunol., 2008, v. 26, p. 513-533.Palic D., Andreasen C.B., Ostojic J. et al. Zebrafish (Danio rerio) whole kidney assays to measure neutrophil extracellular trap release and degranulation of primary granules. J. Immunol. Methods, 2007, v. 319, p. 87-97.Pattison D.I. and Davies M.J. Reactions of myeloperoxidasederived oxidants with biological substrates: gaining chemical insight into human inflammatory diseases. Curr. Med. Chem., 2006, v. 13, p. 3271-3290.Puyet A., Greenberg B. and Lacks S.A. Genetic and structural characterization of end A. A membrane bound nuclease required for transformation of Streptococcus pneumoniae. J. Mol. Biol., 1990, v. 213, p. 727-738.Segal A. How neutrophils kill microbes. Annu. Rev. Immunol., 2005, v. 23, p. 197-223.Sengelov H., Follin P., Kjeldsen L. et al. Mobilization of granules and secretory vesicles during in vivo exudation of human neutrophils. J. Immunol., 1995, v. 154, p. 4157-4165.Serbina N.V., Jia T., Hohl T.M. and Pamer E.G. Monocytemediated defense against microbial pathogens. Ann. Rev. Immunol., 2008, v. 26, p. 421-452.Sumby P., Barbian K.D., Gardner D.J. et al. Extracellular deoxyribonuclease made by group A Streptococcus assists pathogenesis by enhancing evasion of the innate immune response. Proc. Natl. Acad. Sci. USA, 2005, v. 102, p. 1679-1684.Trowbridge H.O. and Emling R. Inflammation: a review of the process. 5ed., Сhicago, Quintessence Publishing Co, Inc., 1997.Urban C.F., Reichard U., Brinkmann V. and Zychlinsky A. Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol., 2006, v. 8, p. 668-676.Vitkov L., Klappacher M., Hannig M. and Krautgartner W.D. Extracellular neutrophil traps in periodontitis. J. Periodont. Res., 2009, v. 44, p. 664-672.Wang Y., Li M., Stadler S. et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J. Cell Biol., 2009, v. 184, p. 205-213.Wassenaar T.M., Engelskirchen M., Park S. and Lastovica A. Differential uptake and killing potential of Campylobacter jejuni by human peripheral monocytes/macrophages. Med. Microbiol. Immunol., 1997, v. 186, p. 139-144.Weinrauch Y., Drujan D., Shapiro S.D. et al. Neutrophil elastase targets virulence factors of enterobacteria. Nature, 2002, v. 417, p. 91-94.Yost C.C., Cody M.J., Harris E.S. et al. Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood, 2009, v. 113, p. 6419-6427.