mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-EOB-2008mimmun-2008Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESЭффект β-аланина на гуморальный иммунный ответ в низкодозовой модели аллергииEffect of β-alanine on humoral immune response in low-dose allergy modelhttps://orcid.org/0000-0003-2143-9824ЧудаковД. Б.ChudakovD. B.

Чудаков Дмитрий Борисович – младший научный сотрудник лаборатории клеточных взаимодействий

117997, Москва, ул. Миклухо-Маклая, 16/10

Chudakov Dmitrii B., Junior Research Associate, Laboratory of Cell Interactions

117997, Moscow, Miklukho-Maklay str., 16/10

boris-chudakov@yandex.ruhttps://orcid.org/0000-0002-7765-8324КоцареваО. Д.KotsarevaO. D.

к.б.н., младший научный сотрудник лаборатории клеточных взаимодействий

Москва

PhD (Biology), Junior Research Associate, Laboratory of Cell Interactions

Moscow

olga.kotsareva@gmail.comЦарегородцеваД. С.TsaregorotsevaD. S.

студентка

Москва

Student

Moscow

tsaregorotseva.daria@yandex.ruhttps://orcid.org/0000-0002-5107-4910КаширинаЕ. И.KashirinaE. I.

к.б.н., инженер-исследователь лаборатории клеточных взаимодействий

Москва

PhD (Biology), Research Engineer, Laboratory of Cell Interactions

Moscow

helen-kas@mail.ruhttps://orcid.org/0000-0002-9043-777XФаттаховаГ. В.FattakhovaG. V.

к.б.н., младший научный сотрудник лаборатории клеточных взаимодействий

Москва

PhD (Biology), Junior Research Associate, Laboratory of Cell Interactions

Moscow

gfattakhova@yahoo.comФГБУН «Институт биоорганической химии имени академиков М.М. Шемякина и Ю.А. Овчинникова» Российской академии наукРоссияM. Shemyakin and Yu. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesRussian FederationФГАОУ ВО «Первый Московский государственный медицинский университет имени И.М. Сеченова» Министерства здравоохранения РФ (Сеченовский университет)РоссияFirst Moscow State I. Sechenov Medical University (Sechenov University)Russian Federation202126022021231127136Copyright © Чудаков Д.Б., Коцарева О.Д., Царегородцева Д.С., Каширина Е.И., Фаттахова Г.В., 20212021Чудаков Д.Б., Коцарева О.Д., Царегородцева Д.С., Каширина Е.И., Фаттахова Г.В.Chudakov D.B., Kotsareva O.D., Tsaregorotseva D.S., Kashirina E.I., Fattakhova G.V.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/2008

В настоящее время усилия многих научных групп в мире направлены на поиск новых факторов, запускающих процесс аллергической сенсибилизации, связанный с синтезом IgE в ответ на безвредные аллергены. По современным данным, продукция тканевых цитокинов индуцируется в тканях через алармины, что, в свою очередь, вызывает проаллергический иммунный ответ. Ранее мы показали, что β-аланин может быть потенциальным алармином, способным стимулировать продукцию тканевых цитокинов. Целью настоящей работы было определение вклада β-аланина в гуморальный иммунный ответ на модели низкодозной аллергии. Мышей BALB/c иммунизировали в область холки рекомбинантным белком Asp f 2 или коммерческим овальбумином (OVA) три раза в неделю с добавкой β-аланина или без него. Чтобы уточнить эффект β-аланина, его сравнивали с действием α-L-аланина – изомера, который не является лигандом рецептора MrgD, а также β-аминоизобутирата, сходного по аффинности к MrgD с β-аланином. Согласно нашим данным, β-аланин стимулировал специфическую продукцию IgE и IgG1 при кратковременном курсе (7 иммунизаций) и повышенное сродство антител после долгосрочной иммунизации (14 инъекций) при использовании менее иммуногенного белка Asp f 2. В случае применения высокоиммунного белка OVA, вклад β-аланина был значимым только в плане аффинности антител. Таким образом, β-аланин ускоряет продукцию специфического IgE в случае применения белка с низкой иммуногенностью. Вклад β-аланина в продукцию специфического IgE не был связан с активацией специфического рецептора MrgD, поскольку β-аминоизобутират – другой лиганд этого рецептора – не оказывал сходного эффекта на гуморальный иммунный ответ. Воздействие β-аланина на продукцию IgG1 также представляется независимым от рецептора MrgD, поскольку α-L-аланин – известная протеиногенная аминокислота также повышала продукцию специфического IgG1. Эффект β-аланина на гуморальный иммунный ответ может быть связан с его неспецифическим действием, например, с его способностью вызывать окислительный стресс путем блокады тауринового транспортера, или со способностью стимулировать клеточный метаболизм.

At the present time, the efforts of many research groups around the world are aimed at finding new factors triggering the allergic sensitization process linked with IgE synthesis to harmless allergens. According to the recent data, production of tissue cytokines is induced in tissue cells by alarmins, thus, in turn, eliciting pro-allergic immune response. Previously we have shown that β-alanine could be a potential alarmin capable to stimulate production of tissue cytokines. The aim of this work was to determine the impact of β-alanine on humoral immune response in low-dose allergy model. BALB/c mice were immunized by recombinant Asp f 2 protein or commercial ovalbumin (OVA) in the withers 3 times a week with or without β-alanine supplementation. To determine the mechanism of β-alanine effect, α-L-alanine, an isomer which is not MrgD receptor ligand, and β-aminoisobutyrate with β-alanine-like affinity to MrgD ligand, were compared. According to our data, β-alanine stimulated specific IgE and IgG1 production in a short-term course (7 immunizations) and enhanced antibody affinity after long-term (14 immunizations) protocol in the case of low-immunogenic protein Asp f 2. In the case of high-immunogenic OVA protein, the impact of β-alanine was significant only upon antibody affinity. Hence, β-alanine accelerates specific IgE production in the case of low-immunogenic protein. The impact of β-alanine on specific IgE production was not linked to specific MrgD receptor activation, because β-aminoisobutyrate, which is the other ligand of this receptor, did not have a similar effect upon humoral immune response. The effect of β-alanine on IgG1 production seems also independent of MrgD receptor, since the common proteinogenic amino acid α-L-alanine also enhanced specific IgG1 production. The effect of β-alanine on humoral immune response could be linked to its non-specific action, e.g., due to its ability to induce oxidative stress through blocking taurine transporter, or due to its ability to stimulate cellular metabolism.

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