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CD14 Mediates Binding of High Doses of LPS but Is Dispensable for TNF-alpha Production
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
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2013 (English)In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, 824919- p.Article in journal (Refereed) Published
Abstract [en]

Activation of macrophages with lipopolysaccharide (LPS) involves a sequential engagement of serum LPS-binding protein (LBP), plasma membrane CD14, and TLR4/MD-2 signaling complex. We analyzed participation of CD14 in TNF-alpha production stimulated with 1-1000 ng/mL of smooth or rough LPS (sLPS or rLPS) and in sLPS binding to RAW264 and J744 cells. CD14 was indispensable for TNF-alpha generation induced by a low concentration, 1 ng/mL, of sLPS and rLPS. At higher doses of both LPS forms (100-1000 ng/mL), TNF-alpha release required CD14 to much lower extent. Among the two forms of LPS, rLPS-induced TNF-alpha production was less CD14-dependent and could proceed in the absence of serumas an LBP source. On the other hand, the involvement of CD14 was crucial for the binding of 1000 ng/mL of sLPS judging from an inhibitory effect of the anti-CD14 antibody. The binding of sLPS was also strongly inhibited by dextran sulfate, a competitive ligand of scavenger receptors (SR). In the presence of dextran sulfate, sLPS-induced production of TNF-alpha was upregulated about 1.6-fold. The data indicate that CD14 together with SR participates in the binding of high doses of sLPS. However, CD14 contribution to TNF-alpha production induced by high concentrations of sLPS and rLPS can be limited.

Place, publisher, year, edition, pages
2013. 824919- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-218352DOI: 10.1155/2013/824919ISI: 000329736000001OAI: oai:DiVA.org:uu-218352DiVA: diva2:695426
Available from: 2014-02-11 Created: 2014-02-11 Last updated: 2014-02-11Bibliographically approved

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Björkelund, Hanna
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