RT info:eu-repo/semantics/article
T1 A Phosphatidylinositol Species Acutely Generated by Activated Macrophages Regulates Innate Immune Responses
A1 Gil de Gómez, Luis
A1 Astudillo, Alma M.
A1 Meana González, Clara
A1 Rubio, Julio M.
A1 Guijas Maté, Carlos
A1 Balboa García, María Ángeles
A1 Balsinde Rodríguez, Jesús
K1 Bioquímica
K1 Inmunología
K1 Biología molecular
K1 Citología
K1 2302 Bioquímica
K1 2412 Inmunología
K1 2302.21 Biología Molecular
AB Activation of macrophages with stimuli of the innate immune response results in the intense remodeling of arachidonate-containing phospholipids, leading to the mobilization of large quantities of this fatty acid for conversion into biologically active eicosanoids. As a consequence of this process, the arachidonate levels in membrane phospholipids markedly decrease. We have applied mass spectrometry-based lipid profiling to study the levels of arachidonate-containing phospholipids under inflammatory activation of macrophages. We identify an unusual inositol phospholipid molecule, PI(20:4/20:4), the levels of which do not decrease but actually increase by 300% after activation of the macrophages. PI(20:4/20:4) is formed and degraded rapidly, suggesting a role for this molecule in regulating cell signaling events. Using a metabolipidomic approach consisting in exposing the cells to deuterium-labeled arachidonate at the time they are exposed to stimuli, we show that PI(20:4/20:4) biosynthesis occurs via the sequential incorporation of arachidonate, first into the sn-2 position of a preformed phosphatidylinositol (PI) molecule, followed by the rapid introduction of a second arachidonate moiety into the sn-1 position. Generation requires the participation of cytosolic phospholipase A2α and CoA-dependent acyltransferases. PI(20:4/20:4) formation is also detected in vivo in murine peritonitis exudates. Elevating the intracellular concentration of PI(20:4/20:4) by introducing the lipid into the cells results in enhancement of the microbicidal capacity of macrophages, as measured by reactive oxygen metabolite production and lysozyme release. These findings suggest that PI(20:4/20:4) is a novel bioactive inositol phospholipid molecule that regulates innate immune responses in macrophages.
PB American Association of Immunologists
SN 0022-1767
YR 2013
FD 2013
LK https://uvadoc.uva.es/handle/10324/79488
UL https://uvadoc.uva.es/handle/10324/79488
LA eng
NO Journal of Immunology, May 2013, vol. 190, n.10, p. 5169-77
NO Producción Científica
DS UVaDOC
RD 23-mar-2026