Macrophages are mononuclear phagocytes which derive either from blood-borne monocytes
or reside as resident macrophages in peripheral (Kupffer cells of the liver, marginal zone
macrophages of the spleen, alveolar macrophages of the lung) and central tissue (microglia). They occur
as M1 (pro-inflammatory; classic) or M2 (anti-inflammatory; alternatively activated) phenotypes.
Macrophages possess P2X7 receptors (Rs) which respond to high concentrations of extracellular
ATP under pathological conditions by allowing the non-selective fluxes of cations (Na+, Ca2+, K+).
Activation of P2X7Rs by still higher concentrations of ATP, especially after repetitive agonist application,
leads to the opening of membrane pores permeable to ~900 Da molecules. For this effect an
interaction of the P2X7R with a range of other membrane channels (e.g., P2X4R, transient receptor
potential A1 [TRPA1], pannexin-1 hemichannel, ANO6 chloride channel) is required. Macrophagelocalized
P2X7Rs have to be co-activated with the lipopolysaccharide-sensitive toll-like receptor 4
(TLR4) in order to induce the formation of the inflammasome 3 (NLRP3), which then activates the
pro-interleukin-1 (pro-IL-1)-degrading caspase-1 to lead to IL-1 release. Moreover, inflammatory
diseases (e.g., rheumatoid arthritis, Crohn’s disease, sepsis, etc.) are generated downstream of
the P2X7R-induced upregulation of intracellular second messengers (e.g., phospholipase A2, p38
mitogen-activated kinase, and rho G proteins). In conclusion, P2X7Rs at macrophages appear to be
important targets to preserve immune homeostasis with possible therapeutic consequences.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89103 |
| Date | 17 January 2024 |
| Creators | Ren, Wenjing, Rubini, Patrizia, Tang, Yong, Engel, Tobias, Illes, Peter |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 232 |
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