Serum CRP interacts with SPARC and regulate immune response in severe cases of COVID-19 infection

Chengyang Liu; Chenyang Zheng; Xipeng Shen; Ling Liang; Qiuyu Li

doi:10.3389/fimmu.2023.1259381

Serum CRP interacts with SPARC and regulate immune response in severe cases of COVID-19 infection

Front Immunol. 2023 Nov 23:14:1259381. doi: 10.3389/fimmu.2023.1259381. eCollection 2023.

Authors

Chengyang Liu¹, Chenyang Zheng², Xipeng Shen², Ling Liang³, Qiuyu Li⁴

Affiliations

¹ Department of Pathology, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking-Tsinghua Center for Life Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.
² School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
³ Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
⁴ Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, China.

Abstract

Serum C-reactive protein (CRP) has been found elevated during COVID-19 infection, and associated with systematic inflammation as well as a poor clinical outcome. However, how did CRP participated in the COVID-19 pathogenesis remains poorly understood. Here, we report that serum C-reactive protein (CRP) levels are correlated with megakaryocyte marker genes and could regulate immune response through interaction with megakaryocytes. Molecular dynamics simulation through ColabFold showed a reliable interaction between monomeric form of CRP (mCRP) and the secreted protein acidic and rich in cysteine (SPARC). The interaction does not affect the physiological activities of SPARC while would be disturbed by pentamerization of CRP. Interplay between SPARC and mCRP results in a more intense immune response which may led to poor prognosis. This study highlights the complex interplay between inflammatory markers, megakaryocytes, and immune regulation in COVID-19 and sheds light on potential therapeutic targets.

Keywords: C-reactive protein; COVID-19; cytokine response storm; megakaryocyte; secreted protein acidic and rich in cysteine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

C-Reactive Protein* / metabolism
COVID-19*
Cells, Cultured
Humans
Inflammation / metabolism
Osteonectin / genetics

Substances

C-Reactive Protein
Osteonectin
SPARC protein, human
CRP protein, human

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the following grants to QL including National Natural Science Foundation of China (No. 81900641) and the Fundamental Research Funds for the Central University: the Research Funding of PKU (BMU2021MX020, BMU2022MX008).