The priming effect of extracellular UTP on human neutrophils: Role of calcium released from thapsigargin-sensitive intracellular stores |
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Authors: | Florin?Tuluc Ovidiu?Bredetean Eugen?Brailoiu John?Meshki Analia?Garcia Nae?J?Dun Email author" target="_blank">Satya?P?KunapuliEmail author |
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Institution: | (1) Department of Physiology, Temple University Medical School, Philadelphia, Pennsylvania, USA;(2) Department of Pharmacology, Temple University Medical School, Philadelphia, Pennsylvania, USA;(3) Department of Physiology, Temple University Medical School, 3420 N. Broad Street, OMS 224, Philadelphia, PA 19140, USA |
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Abstract: | P2Y2 receptors, which are equally responsive to ATP and UTP, can trigger intracellular signaling events, such as intracellular
calcium mobilization and mitogen-activated protein (MAP) kinase phosphorylation in polymorphonuclear leukocytes (PMN). Moreover,
extracellular nucleotides have been shown to prime chemoattractant-induced superoxide production. The aim of our study was
to investigate the mechanism responsible for the priming effect of extracellular nucleotides on reactive oxygen species (ROS)
production induced in human neutrophils by two different chemoattractants: formyl-methionyl-leucyl-phenylalanine (fMLP) and
interleukin-8 (IL-8). Nucleotide-induced priming of ROS production was concentration- and time-dependent. When UTP was added
to neutrophil suspensions prior to chemoattractant, the increase of the response reached the maximum at 1 min of pre-incubation
with the nucleotide. UTP potentiated the phosphorylation of p44/42 and p38 MAP kinases induced by chemoattractants, however
the P2 receptor-mediated potentiation of ROS production was still detectable in the presence of a SB203580 or U0126, supporting
the view that MAP kinases do not play a major role in regulating the nucleotide-induced effect. In the presence of thapsigargin,
an inhibitor of the ubiquitous sarco-endoplasmic reticulum Ca2+-ATPases in mammalian cells, the effect of fMLP was not affected, but UTP-induced priming was abolished, suggesting that the
release of calcium from thapsigargin-sensitive intracellular stores is essential for nucleotide-induced priming in human neutrophils. |
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Keywords: | calcium mitogen-activated protein kinases neutrophil P2Y receptors reactive oxygen species |
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