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Published on: December 28, 2014
Serum Proteomics Identified TAFI as a Potential Molecule Facilitating the Migration of Peripheral Monocytes to
Yuhan Wang1, Wenchao Cheng1, Xiuying Chen2
1Department of Neurology, Xinqiao Hospital, The Army Medical University (Third Military Medical University), Chongqing, China.
Abstract:
Neuroinflammation is assumed as the critical pathophysiologic mechanism of white matter lesions (WMLs), and infiltrated peripheral monocyte-derived macrophages are implicated in the development of neuroinflammation. This study sought to explore the blood molecules that promote the migration of peripheral monocytes to the sites of WMLs. The serum protein expression profiles of patients and Sprague-Dawley rat models with WMLs were detected by data-independent acquisition (DIA) proteomics technique. Compared with corresponding control groups, we acquired 62 and 41 differentially expressed proteins (DEPs) in the serum of patients and model rats with WMLs respectively. Bioinformatics investigations demonstrated that these DEPs were linked to various Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms involved in neuroinflammation. Afterward, we identified thrombin-activatable fibrinolysis inhibitor (TAFI) as a shared and overexpressed protein in clinical and animal serum samples, which was further verified by enzyme-linked immunosorbent assay. Additionally, an upregulation of TAFI was also observed in the white matter of rat models, and the inhibition of TAFI impeded the migration of peripheral monocytes to the area of WMLs. In vitro experiments suggested that TAFI could enhance the migration ability of RAW264.7 cells and increase the expression of Ccr2. Our study demonstrates that neuroinflammatory signals can be detected in the peripheral blood of WMLs patients and model rats. TAFI may serve as a potential protein that promotes the migration of peripheral monocytes to WMLs regions, thereby providing a novel molecular target for further investigation into the interaction between the central and peripheral immune systems.
Insights
This study identifies thrombin-activatable fibrinolysis inhibitor (TAFI) as a key blood molecule promoting monocyte migration to white matter lesions (WMLs). Inhibiting TAFI reduced this migration, suggesting TAFI as a potential therapeutic target for neuroinflammation.
Area of Science:
- Neuroscience
- Immunology
- Proteomics
Background:
- Neuroinflammation is central to white matter lesions (WMLs).
- Peripheral monocyte-derived macrophages contribute to neuroinflammation in WMLs.
- Identifying blood molecules that guide monocytes to WMLs is crucial.
Purpose of the Study:
- To discover circulating proteins that facilitate peripheral monocyte migration to WMLs.
- To investigate the role of thrombin-activatable fibrinolysis inhibitor (TAFI) in this process.
Main Methods:
- Data-independent acquisition (DIA) proteomics to analyze serum protein profiles in WMLs patients and rat models.
- Bioinformatics analysis of differentially expressed proteins (DEPs).
- Enzyme-linked immunosorbent assay (ELISA) and in vitro cell migration assays.
Main Results:
- Identified 62 DEPs in patients and 41 in rat models, linked to neuroinflammation pathways.
- Thrombin-activatable fibrinolysis inhibitor (TAFI) was consistently upregulated in serum and white matter of WMLs models.
- TAFI inhibition reduced monocyte migration to WMLs, and TAFI enhanced RAW264.7 cell migration and Ccr2 expression in vitro.
Conclusions:
- Neuroinflammatory signals are detectable in peripheral blood of WMLs patients and models.
- TAFI promotes peripheral monocyte migration to WMLs, acting as a potential molecular target.
- This highlights a novel link between central and peripheral immune systems in WMLs pathogenesis.
