mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-POF-1954mimmun-1954Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПродукция факторов, участвующих в регуляции фиброза, различными типами макрофагов человекаProduction of factors involved into fibrosis regulation by various types of human macrophageshttps://orcid.org/0000-0003-0884-0226МаксимоваА. А.MaksimovaA. A.

Александра Александровна Максимова – аспирант лаборатории клеточной иммунотерапии.

630099, Новосибирск, ул. Ядринцевская, 14, Тел.: 8 (383) 222-26-74, Факс: 8 (383) 222-70-28

Maksimova Aleksandra A. - Postgraduate Student,  Laboratory of Cellular Immunotherapy.

parkinson.dses@gmail.comШевелаЕ. Я.ShevelaE. Ya.

Шевела Екатерина Яковлевна  – доктор медицинских наук, ведущий научный сотрудник лаборатории клеточной иммунотерапии.

PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy.

shevelak@mail.ruСахноЛ. В.SakhnoL. V.

Сахно Людмила Васильевна  – кандидат биологических наук,  старший научный сотрудник лаборатории клеточной иммунотерапии.

PhD (Biology), Senior Research Associate, Laboratory of Cellular Immunotherapy.

lsahno53@mail.ruОстанинА. А.OstaninA. A.

Останин Александр Анатльевич – доктор медицинских наук, профессор, главный научный сотрудник лаборатории клеточной иммунотерапии.

PhD, MD (Medicine), Professor, Main Research Associate, Laboratory of Cellular Immunotherapy.

ostanin62@mail.ruЧерныхЕ. Р.ChernykhE. R.

Елена Рэмовна Черных – доктор медицинских наук, профессор, член-корр. РАН, заведующая  лабораторией лаборатории клеточной иммунотерапии.

Новосибирск

PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Laboratory of Cellular Immunotherapy.

ct_lab@mail.ruФГБНУ Научно-исследовательский институт фундаментальной и клинической иммунологииРоссияResearch Institute of Fundamental and Clnical ImmunologyRussian Federation202005082020224625632Copyright © Максимова А.А., Шевела Е.Я., Сахно Л.В., Останин А.А., Черных Е.Р., 20202020Максимова А.А., Шевела Е.Я., Сахно Л.В., Останин А.А., Черных Е.Р.Maksimova A.A., Shevela E.Y., Sakhno L.V., Ostanin A.A., Chernykh E.R.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/1954

Macrophages (Mφ) play a key role in regulation of fibrogenesis, including proliferation of fibroblasts and  myofibroblasts, differentiation of progenitor cells into  myofibroblasts, as well as synthesis  and  secretion of the  extracellular matrix, mainly  collagen.  The  direction of the  Mφ effects (stimulation or suppression)  is determined by a number of factors,  including the stage of the fibrotic process and the Mφ functional phenotype dependent on the signals of microenvironment. One  of the feasible ways of the fibrogenesis  regulating is the secretion of pro-  or antifibrotic factors such as matrix metalloproteinases, inhibitors of metalloproteinases and some cytokines. However, existing data on ability to secrete  these factors by various subpopulations of human Mφ are rare and controversial. The aim of this study was to characterize the ability of human M1,  M2a,  and M2c Mφ differentiating in the presence of GM-CSF to produce matrix metalloproteinases (MMP-9) and their tissue inhibitors (TIMP-1), as well as some cytokines and growth factors. As compared to M2 macrophages, the M1 macrophages polarized by lipopolysaccharide produced significantly  more TNFα, IL-6 and IL-2 that have pro-inflammatory activity and are able to initiate a fibrotic process.  In turn,  M2a Mφ stimulated by IL-4  were characterized by a high level of VEGF production and, at the same time, low levels of TNFα and IL-6, which may determine the important role of these cells at the proliferative stage of fibrosis and stimulation of extracellular matrix deposition. Finally, M2c Mφ polarized by dexamethasone, exhibited  the М2а-like cytokine profile, i.e., VEGF was actively produced against the background of low TNFα and IL-6 synthesis.  Moreover, all three Mφ subpopulations did actively secrete MMP-9 and TIMP-1, without significant  difference in production of these factors. However, M2c Mφ differed by a significantly  higher MMP-9/TIMP-1 ratio index compared to M1 and M2a Mφ, and it is crucial  at the rearrangement stage of the fibrotic  process.  Thus,  the production of MMP-9 and TIMP-1, together with other  pleiotropic cytokines and growth factors by various Mφ subtypes may reflect their role in regulation of fibrotic process at various stages.

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