55 research outputs found
Differential fMet-Leu-Phe- and Platelet-activating Factor-induced Signaling Toward Ral Activation in Primary Human Neutrophils
We have measured the activation of the small GTPase
Ral in human neutrophils after stimulation with fMet-
Leu-Phe (fMLP), platelet activating factor (PAF), and
granulocyte macrophage-colony stimulating factor and
compared it with the activation of two other small
GTPases, Ras and Rap1. We found that fMLP and PAF,
but not granulocyte macrophage-colony stimulating factor,
induce Ral activation. All three stimuli induce the
activation of both Ras and Rap1. Utilizing specific inhibitors
we demonstrate that fMLP-induced Ral activation
is mediated by pertussis toxin-sensitive G-proteins and
partially by Src-like kinases, whereas fMLP-induced
Ras activation is independent of Src-like kinases. PAFinduced
Ral activation is mediated by pertussis toxininsensitive
proteins, Src-like kinases and phosphatidylinositol
3-kinase. Phosphatidylinositol 3-kinase is not
involved in PAF-induced Ras activation. The calcium
ionophore ionomycin activates Ral, but calcium depletion
partially inhibits fMLP- and PAF-induced Ral activation,
whereas Ras activation was not affected. In addition,
12-O-tetradecanoylphorbol-13-acetate-induced
activation of Ral is completely abolished by inhibitors of
protein kinase C, whereas 12-O-tetradecanoylphorbol-
13-acetate-induced Ras activation is largely insensitive.
We conclude that in neutrophils Ral activation is mediated
by multiple pathways, and that fMLP and PAF induce
Ral activation differently
Comparison of the roles of mitogen-activated protein kinase kinase and phosphatidylinositol 3-kinase signal transduction in neutrophil effector function
Although it is known that many stimuli can activate mitogen-
activated protein kinases (MAPKs) and phosphatidylinositol 3-
kinases (PI3K) in human neutrophils, little is known concerning
either the mechanisms or function of this activation. We have
utilized a selective inhibitor of MAPKkinase (MEK), PD098059,
and two inhibitors of PI3K, wortmannin and LY294002, to
investigate the roles of these kinases in the regulation of
neutrophil effector functions. Granulocyte/macrophage colony-
stimulating factor, platelet-activating factor (PAF) and N-for-
mylmethionyl-leucyl-phenylalanine are capable of activating
both p44^(ERK1) and p42^(ERK2) MAPKs and phosphotyrosine-asso-
ciated PI3K in human neutrophils. The activation of extracellular
signal-related protein kinases (ERKs) is correlated with the
activation of p21^(ras) by both tyrosine kinase and G-protein-
coupled receptors as measured by a novel assay for GTP loading.
Wortmannin and LY294002 inhibit, to various degrees, super-
oxide generation, neutrophil migration and PAF release. In-
cubation with PD098059, however, inhibits only the PAF release
stimulated by serum-treated zymosan. This demonstrates that,
while neither MEK nor ERK kinases are involved in the acti-
vation of respiratory burst or neutrophil migration, inhibition
of PAF release suggests a potential role in the activation of
cytosolic phospholipase A2 . PI3K isoforms, however, seem to
have a much wider role in regulating neutrophil functioning
Inflammatory Disease Processes and Interactions with Nutrition
Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain ω-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (ω-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are require
Apparent influences of host plant distribution on the structure and the genetic variability of local populations of the Purple Clay (Diarsia brunnea).
International audienc
Chemically mediated burrow recognition in the Mexican tarantula Brachypelma vagans female
International audienc
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