New insights into endotoxin-induced activation of macrophages: involvement of a K+ channel in transmembrane signaling - PubMed (original) (raw)
New insights into endotoxin-induced activation of macrophages: involvement of a K+ channel in transmembrane signaling
R Blunck et al. J Immunol. 2001.
Abstract
LPS (endotoxins) activate cells of the human immune system, among which are monocytes and macrophages, to produce endogenous mediators. These regulate the immune response, but may also cause severe harm leading to septic shock. The activation of monocytes/macrophages by LPS is mediated by a membrane-bound LPS receptor, mCD14. As mCD14 lacks a transmembrane domain, a further protein is required for the signal transducing step to the cell interior. Here we show, using excised outside-out membrane patches, that activation of a high-conductance Ca(2+)- and voltage-dependent potassium channel is an early step in the transmembrane signal transduction in macrophages. The channel is activated by endotoxically active LPS in a dose-dependent manner. Channel activation can be completely inhibited by LPS antagonists and by anti-CD14 Abs. Activation of the channel is essential for LPS-induced cytokine production as shown by its inhibition by selective K(+) channel blockers.
Similar articles
- The role of membrane-bound LBP, endotoxin aggregates, and the MaxiK channel in LPS-induced cell activation.
Müller M, Scheel O, Lindner B, Gutsmann T, Seydel U. Müller M, et al. J Endotoxin Res. 2003;9(3):181-6. doi: 10.1179/096805103125001595. J Endotoxin Res. 2003. PMID: 12831460 - A K+ channel is involved in LPS signaling.
Seydel U, Scheel O, Müller M, Brandenburg K, Blunck R. Seydel U, et al. J Endotoxin Res. 2001;7(3):243-7. J Endotoxin Res. 2001. PMID: 11581578 - Phospholipids inhibit lipopolysaccharide (LPS)-induced cell activation: a role for LPS-binding protein.
Mueller M, Brandenburg K, Dedrick R, Schromm AB, Seydel U. Mueller M, et al. J Immunol. 2005 Jan 15;174(2):1091-6. doi: 10.4049/jimmunol.174.2.1091. J Immunol. 2005. PMID: 15634934 - Molecular basis of endotoxin toxicity.
Seydel U. Seydel U. Ann N Y Acad Sci. 1998 Jun 30;851:406-7. doi: 10.1111/j.1749-6632.1998.tb09015.x. Ann N Y Acad Sci. 1998. PMID: 9668631 Review. No abstract available. - Lipopolysaccharide receptors and signal transduction pathways in mononuclear phagocytes.
Chen TY, Lei MG, Suzuki T, Morrison DC. Chen TY, et al. Curr Top Microbiol Immunol. 1992;181:169-88. doi: 10.1007/978-3-642-77377-8_6. Curr Top Microbiol Immunol. 1992. PMID: 1385048 Review.
Cited by
- Editorial: The key role of lipids in the regulation of ion channels.
Saponaro A, Lolicato M. Saponaro A, et al. Front Physiol. 2022 Sep 7;13:1000082. doi: 10.3389/fphys.2022.1000082. eCollection 2022. Front Physiol. 2022. PMID: 36160863 Free PMC article. No abstract available. - Studying KcsA Channel Clustering Using Single Channel Voltage-Clamp Fluorescence Imaging.
McGuire H, Blunck R. McGuire H, et al. Front Physiol. 2022 Jun 3;13:863375. doi: 10.3389/fphys.2022.863375. eCollection 2022. Front Physiol. 2022. PMID: 35721536 Free PMC article. - Deficiency of Cathelicidin Attenuates High-Fat Diet Plus Alcohol-Induced Liver Injury through FGF21/Adiponectin Regulation.
Li F, Chen J, Liu Y, Gu Z, Jiang M, Zhang L, Chen SY, Deng Z, McClain CJ, Feng W. Li F, et al. Cells. 2021 Nov 27;10(12):3333. doi: 10.3390/cells10123333. Cells. 2021. PMID: 34943840 Free PMC article. - The Influence of Bloom Index, Endotoxin Levels and Polyethylene Glycol Succinimidyl Glutarate Crosslinking on the Physicochemical and Biological Properties of Gelatin Biomaterials.
Wu Z, Korntner SH, Olijve J, Mullen AM, Zeugolis DI. Wu Z, et al. Biomolecules. 2021 Jul 9;11(7):1003. doi: 10.3390/biom11071003. Biomolecules. 2021. PMID: 34356627 Free PMC article. - Anti-inflammatory effects of FS48, the first potassium channel inhibitor from the salivary glands of the flea Xenopsylla cheopis.
Deng Z, Zeng Q, Tang J, Zhang B, Chai J, Andersen JF, Chen X, Xu X. Deng Z, et al. J Biol Chem. 2021 Jan-Jun;296:100670. doi: 10.1016/j.jbc.2021.100670. Epub 2021 Apr 15. J Biol Chem. 2021. PMID: 33864815 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous