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Activation of C3 and C5 May Be Involved in the Inflammatory Progression of PCM and GM

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Abstract—

Plasma cell mastitis (PCM) and granulomatous mastitis (GM) are the most common inflammatory diseases constituting nonbacterial mastitis (NBM). However, the pathogenesis of NBM remains unclear. In this study, risk factors for NBM were assessed, as well as the pathological features of PCM and GM. The levels of C3/C3a-C3aR and C5/C5a-C5aR1 of tissues were detected by IHC and WB. Exosomes were isolated from serum and identified by transmission electron microscopy. Then, C3 and C5 levels were detected in peripheral blood, and exosomes were assessed by flow cytometry and immunoelectron microscopy. Obesity and prolonged lactation were risk factors for NBM. The infiltration of plasma cells and lymphocytes around the dilated catheter in PCM and the formation of granulomatous structures in GM were the respective pathological features. C3/C3a-C3aR and C5/C5a-C5aR1 levels were elevated in PCM and GM tissue samples. There were no differences in peripheral blood levels of C3 and C5, while C3a and C5a were highly expressed in exosomes. These results suggest that the complement family is activated in PCM and GM, exosomes enrich C3a and C5a, and mediate the spread of inflammation. These findings provide new insights into the molecular mechanisms of PCM and GM and identify therapeutic targets.

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Acknowledgements

We thank Dakang Sun for Flow cytometry analysis, Song Wang for collecting some clinical data, and Hongliang Dong for transmission electron microscope assistance. Finally, we thank Xiao-yang Xu and Liu Liu who made the professional pathological assistance, including diagnosis and immunohistochemical analysis of PCM and GM.

Funding

This work was supported by the National Natural Science Foundation of China (No. 50012301173, No. 81902702, No. 81173601, and No. 31801085), Natural Science Foundation of Shandong Province (No. ZR2017LH072 and No. ZR2017MH033), Projects of Binzhou technology development program (No. 2015ZC0301), National Key Research and Development Project (No. 2018YFC0114705), Scientific Research Staring Foundation of Binzhou Medical University (No. BY2014KYQD36, No. BY2014KJ36, and No. BY2017KJ01), and Science and Technology Program of Universities in Shandong Province (No. J15LL51).

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Authors and Affiliations

  1. Department of Thyroid and Breast Surgery, Binzhou Medical University Hospital, 661 Huanghe 2nd Road, Binzhou, Shandong, 256603, People’s Republic of China

    Xiao-qiang Li, Hong-guang Sun, Xiao-hong Wang, Hao-jie Zhang, Xiang-sheng Zhang, Yue Yu, Qing-qun Guo & Zhen-lin Yang

  2. Department of Thyroid and Breast Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, 264000, People’s Republic of China

    Jian Liu

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Contributions

Xiaoqiang Li, Xiaohong Wang, and Zhenlin Yang designed the study and performed editing and critical revision of this manuscript. Xiaoqiang Li, Xiaohong Wang, and Hong-guang Sun performed the experiments. Xiaoqiang Li and Yue Yu analyzed the data. Xiaoqiang Li, Qing-qun Guo, and Jian Liu collected and classified the samples. Xiangsheng Zhang and Hao-jie Zhang collected the clinical data. All authors read and approved the final manuscript. Xiaoqiang Li and Hong-guang Sun contributed equally to this work.

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Correspondence to Xiao-hong Wang or Zhen-lin Yang.

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The present study was approved and was obtained from Ethics Committee of Binzhou Medical University (Binzhou, China; approval no. 2018‑19‑01). Written informed consent was obtained from patients prior to enrolment.

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The authors declare no competing interests. This work was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part.

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Xiao-qiang Li and Hong-guang Sun are co-first authors.

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Li, Xq., Sun, Hg., Wang, Xh. et al. Activation of C3 and C5 May Be Involved in the Inflammatory Progression of PCM and GM. Inflammation 45, 739–752 (2022). https://doi.org/10.1007/s10753-021-01580-2

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