| A novel mechanism of cytokine release in phagocytes induced by aggretin, a snake venom C-type lectin protein, through CLEC-2 ligation. | |
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MedLine Citation:
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PMID: 20738764 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Summary Background: Macrophages are major immune cells and play an important role in modulating homeostasis and the immune defense mechanism. In inflammatory responses to the infection of pathogens, macrophages are activated, producing various inflammatory mediators. Snake venom C-type lectin proteins (snaclecs) have diverse targets, including platelet GPVI, GPIb, integrin α2β1 or CLEC-2 expressed in platelets, endothelial cells or myeloid cells. Methods: In this study, murine macrophages (RAW 264.7 cells) and human monocytes (THP-1) were treated with different snaclecs, including aggretin, gramicetin, trowaglerix and convulxin, in the absence or presence of LPS for 24 h. Results: The production of cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), in supernatants was measured by ELISA. Aggretin increased the production of TNF-α and IL-6 in both RAW264.7 and THP-1 cells; however, the other snaclecs did not. Aggretin induced extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) tyrosine phosphorylation of RAW264.7 cells. Pretreatments with inhibitor of ERK, JNK, p38 or NF-κB abolished cytokine release caused by aggretin. Aggretin bound to THP-1 cells in a concentration-dependent manner and it displaced the CLEC-2 mAb binding to THP-1 cells and the immobilized aggretin selectively bound to CLEC-2 of both platelets and THP-1 cell lysates. Furthermore, aggretin elevated the plasma level of IL-6 in ICR mice as it was administered intramuscularly. Conclusion: These results indicate that aggretin may induce cytokine TNF-α/IL-6 release via interacting with CLEC-2 receptor and the subsequent MAPK and NF-κB activation in monocytes/macrophages. |
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Authors:
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C-H Chang; C-H Chung; C-C Hsu; T-Y Huang; T-F Huang |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of thrombosis and haemostasis : JTH Volume: 8 ISSN: 1538-7836 ISO Abbreviation: J. Thromb. Haemost. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2011-01-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101170508 Medline TA: J Thromb Haemost Country: England |
Other Details:
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Languages: eng Pagination: 2563-70 Citation Subset: IM |
Copyright Information:
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© 2010 International Society on Thrombosis and Haemostasis. |
Affiliation:
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Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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