РОЛЬ ГАЗОТРАНСМІТТЕРІВ У РЕАЛІЗАЦІЇ ІМУННИХ РЕАКЦІЙ
Анотація
В огляді проаналізовано відомості стосовно участі молекул нітроген оксиду, дигідроген сульфіду та монооксиду карбону в процесах активації імунної системи, запальних та протизапальних реакціях. Нітроген оксид продукується клітинами імунної системи (NK-клітинами, мастоцитами, дендритними клітинами, фагоцитуючими клітинами) та клітинами, які відіграють важливу роль у реалізації імунної відповіді (епітеліоцити, ендотеліоцити, фібробласти, гладенькі м’язи судин, кератиноцити,
хондроцити, гепатоцити). Фермент, який відповідає за утворення цього газотрансміттеру, це NO-синтаза яка має щонайменше три ізоформи. Експресія ізоформ регулюється продукцією цитокінів, мікробними стимулами, наявністю субстрату – аргініну. Нітроген оксид відіграє значну роль у процесі селекції та розвитку Т-клітин, пригнічує адгезію тромбоцитів та лейкоцитів до ендотелію, порушує процес діапедезу моноцитів і гранулоцитів. У випадку аутоімунних процесів, нітроген оксид
захищає організм від імунопатологічних впливів.
Гідроген сульфід має протизапальні ефекти через пригнічення протизапальних цитокінів, циклооксигенази-2, простагландину Е2. Обробка клітин донорами гідроген сульфіду пригнічує експресію ox-LDL-лектиноподібних рецепторів. Окрім цього, ендогенний та екзогенний гідроген сульфід зменшує утворення атерогенних пінистих клітин. Застосування екзогенного гідроген сульфіду знижує активацію NFκB у макрофагах за допомогою гемоксигеназа-1 – залежного механізму. Незважаючи на те, що переважна більшість досліджень вказує на протизапальні ефекти, має місце збільшення рівня фактору некрозу пухлин-альфа. Актуальним є пошук донорів гідроген сульфіду з метою застосування їх як протизапальних засобів.
Монооксид карбону in vivo утворюється ендогенно в результаті розщеплення гем-вмісних білків. Цей поцес каталізується ферментом гемоксигеназою. Безсумнівним є те, що монооксид карбону за низької концентрації може впливати на клітинні сигнальні шляхи трансдукції, які призводять до модифікації клітинних функцій, формування адаптивних змін. Біологічні властивості низьких концентрацій монооксиду карбону варіюються від регуляції тонусу судин, біогенезу мітохондрій, модуляції запалення,
апоптозу до клітинної проліферації. Для контролю кількості вивільненого монооксиду карбону використовують нові сполуки – донори, які вже проявили свої протизапальні властивості. Гемоксигеназа-1 є ферментом, залученим до реалізації протизапальних функцій цього газотрансміттера.
Посилання
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