Mechanism of neutrophil activation by NAF, a novel monocyte‐derived peptide agonist

Thelen, Marcus; Peveri, Paola; Kernen, Peter; Tscharner, Vinzenz von; Walz, Alfred; Baggiolini, Marco

doi:10.1096/fasebj.2.11.2840318

Cited by 282 publications

(148 citation statements)

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“…The effects, however, are much less pronounced than those observed for neutrophils [2]. We were unable to detect [Ca*']i changes [29] or significant migration responses by human blood lymphocytes challenged with IL-8 (T. Geiser, unpublished results). Our present data show that leukemic T cells are able to migrate, but only respond to CXC chemokines when transfected with cDNAs for one of the IL-8 receptors.…”

Section: Chemotaxismentioning

confidence: 78%

Both interleukin‐8 receptors independently mediate chemotaxis

et al. 1994

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Neutrophil leukocytes, the target cells for interleukin-8 and related CXC chemokines, bear high numbers of two types of IL-8 receptors (IL-8Rl and IL-8R2). By cDNA transfection Jurkat cell lines were generated that stably express either IL-8Rl or IL-8R2 (J-IL8Rl and J-IL8R2). J-IL8Rl expressed 4,000 + 1,000 copies of IL-8R1, and bound IL-8 with high affinity (Kd l-4 nM) and GROcl and NAP-2 with low affinity (Kd 200-500 nM). J-IL8R2 expressed 17,000 f 3,000 copies of IL-8R2, and bound all three chemokines with high affinity. Both transfectants showed a similar degree of chemotactic migration after stimulation with IL-8, GROa and NAP-2. All three chemokines were equally potent as attractants of J-IL8R2, whereas IL-8 was 300 to l,OOO-fold more potent than GROcl or NAP-2 as attractant of J-IL8Rl. The potencies, therefore, agree with the affinities of the ligands to IL-8Rl and IL-8R2. Our results demonstrate that both IL-8 receptors function independently, and mediate chemotaxis in response to IL-8 and other CXC chemokines.

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Section: Chemotaxismentioning

confidence: 78%

Both interleukin‐8 receptors independently mediate chemotaxis

et al. 1994

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“…It activates PMN to degranulate and exhibit respiratory burst [12,13] and is chemotactic for PMN and lymphocytes in vitro and in vivo [2,4,10,14]. Further activities include triggering of histamine and leukotriene release from IL-3-primed basophils [ 151, spasmogenic activity on airway smooth muscle [16], and effects on PMN adherence to endothelial cells [11,17].…”

Section: Introduction 2 Experimentalmentioning

confidence: 99%

Crystallization and preliminary X‐ray crystallographic study of interleukin‐8

et al. 1990

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“…IL-8 induces the mobilization of calcium in neutrophils (24,25), and this may occur through the activation of phospholipase C-␤ (26). There is also evidence that IL-8 stimulates phospholipase D activity (27), phosphatidylinositol-3 kinase (PI3K) activity (28), and GTP loading of RhoA (29) in human neutrophils.…”

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confidence: 99%

Signaling Pathways Involved in IL-8-Dependent Activation of Adhesion Through Mac-1

Takami

Terry

Petruzzelli

2002

The Journal of Immunology

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In human neutrophils, IL-8 induces chemotaxis, the respiratory burst, and granule release, and enhances cellular adhesion, a β2 integrin-dependent event. IL-8 stimulates neutrophil adhesion to purified fibrinogen in a Mac-1-dependent manner. Mitogen-activated protein kinase (MAPK) activation was detected in human neutrophil lysates after treatment with IL-8 and PMA, but not the activating mAb CBR LFA 1/2. IL-8-stimulated neutrophil adhesion to fibrinogen was blocked 50% by the MAPK/extracellular signal-related kinase-activating enzyme inhibitor PD098059. Adhesion was blocked ∼75% by inhibition of the phosphatidylinositol-3 kinase (PI3K) pathway with LY294002, supporting that activation of both MAPK and PI3K may play a role in IL-8-dependent inside-out signals that activate Mac-1. Activation of MAPK was inhibited in IL-8-stimulated cells in the presence of PI3K inhibitors LY294002 or wortmannin, supporting a model in which PI3K is upstream of MAPK. IL-8-stimulated neutrophil adhesion was inhibited 50% by bisindolylmaleimide-I, implicating protein kinase C (PKC) in the intracellular signaling from the IL-8R to Mac-1. A 74-kDa molecular mass species was detected by an activation-specific Ab to PKC when cells were stimulated with PMA or IL-8, but not a β2-activating Ab. Inhibition of either MAPK or PKC resulted in partial inhibition of IL-8-stimulated polymorphonuclear neutrophil adhesion, and treatment with both inhibitors simultaneously completely abolished IL-8-stimulated adhesion to ligand. Inhibition of PI3K blocked MAPK activation, but not PKC activation, suggesting a branch point that precedes PI3K activation. These data suggest that both MAPK and PKC are activated in response to IL-8 stimulation, and that these may represent independent pathways for β2 integrin activation in neutrophils.

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Mechanism of neutrophil activation by NAF, a novel monocyte‐derived peptide agonist

Cited by 282 publications

References 0 publications

Both interleukin‐8 receptors independently mediate chemotaxis

Both interleukin‐8 receptors independently mediate chemotaxis

Crystallization and preliminary X‐ray crystallographic study of interleukin‐8

Signaling Pathways Involved in IL-8-Dependent Activation of Adhesion Through Mac-1

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