mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-SPA-2460mimmun-2460Research ArticleОБЗОРЫREVIEWSСекреторная фосфолипаза А2: биомаркер воспаления аутоиммунных, бактериальных и вирусных заболеванийSecretory phospholipase A2: a biomarker of inflammation in autoimmune, bacterial and viral diseaseshttps://orcid.org/0000-0002-5441-2911УразовС. П.UrazovS. P.

Уразов Станислав Петрович - врач-кардиолог.

197706, Санкт-Петербург, Сестрорецк, ул. Борисова, 9.

Тел.: 8 (906) 276-64-53

Stanislav P. Urazov - Cardiologist, Municipal City Hospital No. 40 of the Kurort Region.

197706, St. Petersburg, Sestroretsk, Borisov str., 9.

Phone: 7 (906) 276-64-53

urasta@list.ruhttps://orcid.org/0000-0003-2464-7370ЧерновА. Н.ChernovA. N.

Чернов Александр Н. — научный сотрудник отдела общей патологии и патологической физиологии.

Санкт-Петербург.

Research Associate, Department of General Pathology and Pathological Physiology, Institute of Experimental Medicine.

St. Petersburg.

al.chernov@mail.ruhttps://orcid.org/0000-0001-9062-966XЧеркасА. В.CherkasA. V.

Черкас Алина В. — инженер-исследователь, лаборатория «Промышленные системы потоковой обработки данных» Центра компетенций Национальной технологической инициативы по направлению «Новые производственные технологии».

Санкт-Петербург.

Research Engineer, Laboratory “Industrial Systems for Streaming Data Processing”, Industrial Systems of Data Flow Treatment, St. Petersburg Polytechnic University.

St. Petersburg.

alina-cherkas@mail.ruhttps://orcid.org/0000-0002-1678-5223БойковА. В.BoikovA. V.

Бойков Алексей В. — ведущий инженер, инженер-исследователь, лаборатория «Промышленные системы потоковой обработки данных» Центра компетенций Национальной технологической инициативы по направлению «Новые производственные технологии».

Санкт-Петербург.

Leading Engineer, Laboratory “Industrial Systems for Streaming Data Processing”, Industrial Systems of Data Flow Treatment, St. Petersburg Polytechnic University.

St. Petersburg.

alexey.boykov@spbpu.comhttps://orcid.org/0000-0002-7465-4504ГлотовО. С.GlotovO. S.

Глотов Олег Сергеевич — кандидат биологических наук, заведующий отделом вирусологических и молекулярно-генетических методов диагностики, Детский научно-клинический центр инфекционных болезней Федерального медико-биологического агентства.

Санкт-Петербург.

PhD (Biology), Head, Department of Virological and Molecular Genetic Methods of Diagnostics, Pediatric Research and Clinical Center of Infectious Diseases.

St. Petersburg.

olglotov@mail.ruhttps://orcid.org/0000-0002-3853-4185АпалькоС. В.ApalkoS. V.

Апалько Светлана В. — кандидат биологических наук, заведующий лабораторией молекулярной диагностики и аналитических методов, начальник НИЛ трансляционной биомедицины.

Сестрорецк, Санкт-Петербург.

PhD (Biology), Head, Laboratory of Molecular Diagnostics and Analytical Methods, Head of Research Laboratory of Translational Biomedicine, Municipal City Hospital No. 40 of the Kurort Region.

Sestroretsk, St. Petersburg.

svetlana.apalko@gmail.comhttps://orcid.org/0000-0002-5100-5229СушенцеваН. Н.SushentsevaN. N.

Сушенцева Наталья Н. — биолог.

Сестрорецк, Санкт-Петербург.

Biologist, Municipal City Hospital No. 40 of the Kurort Region.

Sestroretsk, St. Petersburg.

navicula@yandex.ruhttps://orcid.org/0000-0002-9178-8512ПолковниковаИ. А.PolkovnikovaI. A.

Полковникова Ирина А. — биолог.

Сестрорецк, Санкт-Петербург.

Biologist, Municipal City Hospital No. 40 of the Kurort Region.

Sestroretsk, St. Petersburg.

polkovnikovaia@gb40.ruСмирновВ. В.SmirnovV. V.

Смирнов Владимир В. — кандидат медицинских наук, заведующий клинико-диагностической лабораторией.

Сестрорецк, Санкт-Петербург.

PhD (Medicine), Head, Clinical Diagnostic Laboratory, Municipal City Hospital No. 40 of the Kurort Region.

Sestroretsk, St. Petersburg.

vsmirnov888@gmail.comhttps://orcid.org/0000-0001-5036-1259ЩербакС. Г.ShcherbakS. G.

Щербак Сергей Григорьевич — доктор медицинских наук, профессор, главный врач ГБ № 40 Курортного административного района; заведующий кафедрой последипломного медицинского образования СПбГУ.

Сестрорецк; Санкт-Петербург.

PhD, MD (Medicine), Professor, Chief Physician, Municipal City Hospital No. 40 of the Kurort Region; Head, Department of Postgraduate Medical Education, St. Petersburg State University.

Sestroretsk, St. Petersburg.

sgsherbak@mail.ruГородская больница № 40 Курортного административного районаРоссияMunicipal City Hospital No. 40 of the Kurort RegionRussian FederationИнститут экспериментальной медициныРоссияInstitute of Experimental MedicineRussian FederationЦентр компетенций Национальной технологической инициативы по направлению «Новые производственные технологии» ФГАОУ ВО «Санкт-Петербургский политехнический университет Петра Великого»РоссияIndustrial Systems of Data Flow Treatment, St. Petersburg Polytechnic UniversityRussian FederationДетский научно-клинический центр инфекционных болезней Федерального медико-биологического агентстваРоссияPediatric Research and Clinical Center of Infectious DiseasesRussian FederationГородская больница № 40 Курортного административного района; Санкт-Петербургский государственный университетРоссияMunicipal City Hospital No. 40 of the Kurort Region; St. Petersburg State UniversityRussian Federation202213072022244705728Copyright © Уразов С.П., Чернов А.Н., Черкас А.В., Бойков А.В., Глотов О.С., Апалько С.В., Сушенцева Н.Н., Полковникова И.А., Смирнов В.В., Щербак С.Г., 20222022Уразов С.П., Чернов А.Н., Черкас А.В., Бойков А.В., Глотов О.С., Апалько С.В., Сушенцева Н.Н., Полковникова И.А., Смирнов В.В., Щербак С.Г.Urazov S.P., Chernov A.N., Cherkas A.V., Boikov A.V., Glotov O.S., Apalko S.V., Sushentseva N.N., Polkovnikova I.A., Smirnov V.V., Shcherbak S.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2460

Секреторные фосфолипазы А2 (sPLA2) представляют собой большое суперсемейство ферментов с молекулярной массой 14-19 кДа, включающее 15 групп и более 30 изоформ, принадлежащих к четырем типам: секреторный (sPLA2), цитозольный (cPLA2), кальций-независимый (iPLA2) и липопротеин-ассоциированная фосфолипаза A2 (LP-PLA2, PAF-AH). У млекопитающих обнаружены одиннадцать секреторных sPLA2 (IB, IIA, IIC, IID, IIE, IIF, III, V, X, XIIA и XIIB), выполняющие разносторонние функции и участвующие в патогенезе широкого спектра заболеваний. С одной стороны, sPLA2, гидролизуя фосфолипиды мембран, способствуют элиминации поврежденных, апоп-тотических клеток и оказывают сильное бактерицидное, вируцидное действие, в том числе против антибиотикорезистентных штаммов микроорганизмов. В этом плане использование sPLA2 может представлять новую стратегию терапии бактериальных и вирусных инфекций. С другой стороны, в результате действия sPLA2 на ее субстраты образуются биологически активные молекулы (арахидоновая, лизофосфатидная кислоты, лизофосфолипиды, жирные кислоты, простагландины, лейкотриены, тромбоксаны), которые оказывают сильное воспалительное, детергирующее, коагулирующее действие и повышают проницаемость сосудов. Такая провоспалительная роль sPLA2 обуславливает повышение ее уровней и активности при сердечно-сосудистых, дыхательных, аутоиммунных, метаболических, онкологических, бактериальных и вирусных заболеваниях. В обзоре приводится классификация изоформ sPLA2, рассматриваются их субстраты, регулирующие факторы, биологическое значение и механизмы сильного бактерицидного, вируцидного действия, а также провоспалитель-ной активности при сердечно-сосудистых, дыхательных, аутоиммунных, метаболических, бактериальных и вирусных заболеваниях. Отдельно излагаются механизмы селективного действия sPLA2 в отношении грамположительных и грамотрицательных микроорганизмов. Обсуждаются диагностическая, прогностическая значимость, корреляции повышенных уровней и активности sPLA2 с клиническими симптомами, тяжестью и исходом пациентов с ишемической болезнью сердца (CAD), острым инфарктом миокарда (AMI), атеросклерозом, острым воспалительным повреждением легких (ALI), респираторным дистресс-синдромом (ARDS), хронической обструктивной болезнью легких (COPD), ревматоидным артритом, бронхиальной астмой, бактериальными инфекциями, сепсисом и вирусными (COVID-19) инфекциями. Рассматривается возможность использования sPLA2 в качестве биомаркера тяжести и исхода пациентов с хронической обструктивной болезнью легких, бактериальными инфекциями, сепсисом и вирусными, в том числе COVID-19, инфекциями.

Secretory phospholipases A2 (sPLA2) represent a large superfamily of enzymes with a molecular weight of 14-19 kDa, including 15 groups and more than 30 isoforms belonging to four types: secretory (sPLA2), cytosolic (cPLA2), calcium-independent (iPLA2) and lipoprotein-associated phospholipase A2 (LP-PLA2, PAF-AH). Eleven species of secretory sPLA2s (IB, IIA, IIC, IID, IIE, IIF, III, V, X, XIIA, and XIIB) have been found in mammals, performing versatile functions and participating in the pathogenesis of a wide range of diseases. On the one hand, sPLA2 may promote elimination of damaged, apoptotic cells by hydrolyzing membrane phospholipids, and exerts a strong bactericidal and antiviral properties, including pronounced effects against antibiotic-resistant strains of microorganisms. In this regard, the use of sPLA2 may represent a new strategy for the treatment of bacterial and viral infections. Moreover, due to the action of sPLA2 on its substrates, a number of biologically active molecules (arachidonic, lysophosphatidic acids, lysophospholipids, fatty acids, prostaglandins, leukotrienes, thromboxanes) are formed, which provide strong inflammatory, detergent, coagulating effects and increase vascular permeability. This pro-inflammatory role of sPLA2 may explain its increase levels and activity in cardiovascular, respiratory, autoimmune, metabolic, oncological, bacterial and viral disorders. The review article presents a classification of sPLA2 isoforms, their substrates, regulatory factors, biological significance, and mechanisms of their strong bactericidal, virucidal, and pro-inflammatory activity in the heart and lung disorders, autoimmune, metabolic, bacterial, and viral diseases. In particular, the mechanisms of the selective action of sPLA2 against Gram-positive and Gram-negative microorganisms are discussed. We consider diagnostic and prognostic significance, correlations between elevated levels and activity of sPLA2 and distinct clinical symptoms, severity and outcome in the patients with coronary heart disease (CAD), acute myocardial infarction (AMI), atherosclerosis, acute inflammatory lung injury (ALI), respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, bronchial asthma, bacterial infections, septicemia and viral (COVID-19) infections. The opportunity of using sPLA2 as a biomarker of the severity and outcome of patients with chronic obstructive pulmonary disease, bacterial infections, sepsis and viral infections, including COVID-19, is also considered.

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The authors declare that there are no conflicts of interest present.