Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 7, July, p. 833–840

doi: 10.17219/acem/121924

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Autologous transfusion of “old” red blood cells-induced M2 macrophage polarization through IL-10-Nrf2-HO-1 signaling complexes

Zhen-Zhou Li1,2,A,B,C,D,E, Zi-Wei Zhang3,A,B,C,D, Huan Wang2,B,C,E,F, Yong-Quan Chen2,B,C,E, Xiao-Fang Zhou2,B,C, Li-Shuang Duan2,C,E, Xiao-Xiao Wang2,E, Feng Xu4,E, Jian-Rong Guo1,2,B,F

1 Shanghai Pudong New Area Gongli Hospital Training Base, Ningxia Medical University, China

2 Department of Anesthesiology, Gongli Hospital, Second Military Medical University, Shanghai, China

3 Department of Anesthesiology, Yijishan Hospital, Wannan Medical College, Wuhu, China

4 Department of Anesthesiology, Anhui Province No. 2 People’s Hospital, Hefei, China

Abstract

Background. Red blood cell (RBC) transfusion is associated with systemic inflammation and immune suppression as adverse outcomes.
Objectives. To investigate the immunomodulatory function of the transfused autologous RBC in altering pro-inflammatory and immunosuppressive effects.
Material and Methods. A total of 24 Sprague Dawley male rats were randomly divided into 3 groups (n = 8 in each group). Group 1 did not receive blood transfusions, while the other 2 groups of rats separately received transfusion of RBC stored for 14 days (group 2) and 35 days (group 3). The rats were treated with HO-1 inhibitor, HO-1 inducer and nuclear factor erythroid 2-related factor 2 (Nrf2) activator after they separately received autologous transfusion of RBC that were cryopreserved for 14 days or 35 days. The blood samples of the rats were collected 12 h after the transfusion, and the macrophage phenotype of M1 and M2 were analyzed with flow cytometry (FCM). Also, the surface protein expression of CD68 and CD200R in macrophages were analyzed and the inflammatory signals in the serum were measured with enzyme-linked immunosorbent assay (ELISA). Moreover, the location and expression of proteins heme oxygenase 1 (HO-1), arginine 1 (Arg-1) and nitric oxide synthase 2 (NOS2) in macrophage were detected with immunofluorescence (IF).
Results. Autologous transfusion of long-time stored (“old”) RBC promoted macrophage polarization to M2 phenotype and upregulated the expression of its surface proteins CD68 and CD200R. The pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β, and IL-18 were inhibited, and the secretion of NOS isoforms (iNOS) in serum was reduced with blood transfusion; contrarily, the production of IL-10 and CCL22 was increased. Additionally, HO-1, Arg-1 and NOS2 proteins were located in the cytoplasm, and HO-1 and Arg-1 proteins were highly expressed in macrophage, while the expression of protein NOS2 was low. Moreover, Nrf2, HO-1 and Arg-1 proteins were upregulated in macrophage after receiving “old” RBC transfusion.
Conclusion. Autologous transfusion of “old” RBC drove the macrophage phenotype toward M2 macrophages and induced immunosuppressive effects through the IL-10-NRF2-HO-1 signals.

Key words

immunosuppressive treatment, red blood cell transfusion, M2 macrophage, IL-10-NRF2-HO-1 signals

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