Abstract
Platelet activating factor (PAF) and PAF-like lipids induce inflammatory responses in target cells. These lipid mediators are inactivated by PAF-acetylhydrolase (PAF-AH). The PAF signaling system affects the growth of hematopoietic CD34(+) cells, but roles for PAF-AH in this process are unknown. Here, we investigated PAF-AH function during megakaryopoiesis and found that human CD34(+) cells accumulate this enzymatic activity as they differentiate toward megakaryocytes, consistent with the expression of mRNA and protein for the plasma PAF-AH isoform. Inhibition of endogenous PAF-AH activity in differentiated megakaryocytes increased formation of lipid mediators that signaled the PAF receptor (PAFR) in fully differentiated human cells such as neutrophils, as well as megakaryocytes themselves. PAF-AH also controlled megakaryocyte alpha(IIb)beta(3)-dependent adhesion, cell spreading, and mobility that relied on signaling through the PAFR. Together these data suggest that megakaryocytes generate PAF-AH to modulate the accumulation of intracellular phospholipid mediators that may detrimentally affect megakaryocyte development and function.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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1-Alkyl-2-acetylglycerophosphocholine Esterase / biosynthesis
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1-Alkyl-2-acetylglycerophosphocholine Esterase / genetics
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1-Alkyl-2-acetylglycerophosphocholine Esterase / physiology*
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Calcium Signaling
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Cell Adhesion
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Cells, Cultured / cytology
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Cells, Cultured / drug effects
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Cells, Cultured / metabolism
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Enzyme Induction
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Fetal Blood / cytology
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / enzymology
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Humans
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Interleukin-3 / pharmacology
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Megakaryocytes / cytology
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Megakaryocytes / drug effects
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Megakaryocytes / metabolism*
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Phospholipids / metabolism*
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Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
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Platelet Membrane Glycoproteins / physiology
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RNA, Messenger / biosynthesis
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Receptors, G-Protein-Coupled / physiology
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Stem Cell Factor / pharmacology
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Thrombopoiesis / drug effects
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Thrombopoiesis / physiology*
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Thrombopoietin / pharmacology
Substances
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IL3 protein, human
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Interleukin-3
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Phospholipids
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Platelet Glycoprotein GPIIb-IIIa Complex
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Platelet Membrane Glycoproteins
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RNA, Messenger
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Receptors, G-Protein-Coupled
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Stem Cell Factor
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platelet activating factor receptor
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Thrombopoietin
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1-Alkyl-2-acetylglycerophosphocholine Esterase