The effect of interleukin-8 and granulocyte macrophage colony stimulating factor on the response of neutrophils to formyl methionyl leucyl phenylalanine

Mikami, M.; Llewellyn-Jones, C G; Stockley, Robert A.

doi:10.1016/s0925-4439(98)00040-4

Cited by 9 publications

(4 citation statements)

References 20 publications

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“…Previously it has been demonstrated that IL-8 levels are increased in COPD patients, 15,32 and that increased levels of IL-8 in sputum samples correlate with the airway bacterial load and proteinase released from activated neutrophils. 33…”

Section: Discussionmentioning

confidence: 99%

Serum and bronchial lavage fluid concentrations of IL-8, SLPI, sCD14 and sICAM-1 in patients with COPD and asthma

Hollander

Šitkauskienė²,

Sakalauskas³

et al. 2007

Respiratory Medicine

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Section: Discussionmentioning

confidence: 99%

Serum and bronchial lavage fluid concentrations of IL-8, SLPI, sCD14 and sICAM-1 in patients with COPD and asthma

Hollander

Šitkauskienė²,

Sakalauskas³

et al. 2007

Respiratory Medicine

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“…A recent study demonstrated that whereas activation of PI-3K was essential for fMLP-induced pseudopod extension, IL-8-stimulated pseudopod extension was much less dependent on PI-3K [42]. Furthermore, IL-8-but not fMLP-induced F-actin polymerization, pseudopod extension, and migration have been shown to be enhanced by pretreatment of cells with GM-CSF or insulin [30,42,43]. Moreover, this GM-CSF priming was PI-3K-dependent, whereas priming by insulin was PI-3K-independent.…”

Section: Discussionmentioning

confidence: 99%

Impaired interleukin-8- and GROα-induced phosphorylation of extracellular signal-regulated kinase result in decreased migration of neutrophils from patients with myelodysplasia

Fuhler

Knol

Drayer

et al. 2004

Journal of Leukocyte Biology

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Patients with myelodysplasia suffer from recurrent bacterial infections as a result of differentiation defects of the myeloid lineage and a disturbed functioning of neutrophilic granulocytes. Important physiological activators of neutrophils are the cytokines interleukin-8/CXC chemokine ligand 8 (IL-8/CXCL8), which activates CXC chemokine receptor 1 and 2 (CXCR1 and CXCR2), and growth-related oncogene (GROalpha)/CXCL1, which stimulates only CXCR2. In this study, we show that migration toward IL-8/GROalpha gradients is decreased in myelodysplastic syndrome (MDS) neutrophils compared with healthy donors. We investigated the signal transduction pathways involved in IL-8/GROalpha-induced migration and showed that specific inhibitors for extracellular signal-regulated kinase (ERK)1/2 and phosphatidylinositol-3 kinase (PI-3K) abrogated neutrophil migration toward IL-8/GROalpha. In accordance with these results, we subsequently showed that IL-8/GROalpha-stimulated activation of ERK1/2 was substantially diminished in MDS neutrophils. Activation of the PI-3K downstream target protein kinase B/Akt was disturbed in MDS neutrophils when cells were activated with IL-8 but normal upon GROalpha stimulation. IL-8 stimulation resulted in higher migratory behavior and ERK1/2 activation than GROalpha stimulation, suggesting a greater importance of CXCR1. We then investigated IL-8-induced activation of the small GTPase Rac implicated in ERK1/2-dependent migration and found that it was less efficient in neutrophils from MDS patients compared with healthy donors. In contrast, IL-8 triggered a normal activation of the GTPases Ras and Ral, indicating that the observed defects were not a result of a general disturbance in CXCR1/2 signaling. In conclusion, our results demonstrate a disturbed CXCR1- and CXCR2-induced neutrophil chemotaxis in MDS patients, which might be the consequence of decreased Rac-ERK1/2 and PI-3K activation within these cells.

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“…24 The priming of superoxide production by GM-CSF is widely recognized 32 ; however, the role of GM-CSF in chemotaxis is controversial. 33 There are reports showing that GM-CSF has no significant effect on chemotaxis 34 ; however, other reports show that it either blocks chemotaxis 35 or enhances it. 36 One possibility for the discrepancies in the reported effects of GM-CSF on chemotaxis is the possible involvement of adhesion receptors, which are easily primed.…”

Section: Effect Of Gm-csf and Insulinmentioning

confidence: 99%

Novel pathways of F-actin polymerization in the human neutrophil

Chodniewicz

Zhelev

2003

Blood

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Recently we demonstrated the existence of a phosphatidylinositol 3-kinase (PI3K)-independent F-actin polymerization during neutrophil pseudopod extension. Here we examine the use of the PI3K-dependent and PI3K-independent pathways of activation by the N-formyl peptide receptor and the chemokine receptors, and the priming of the 2 pathways by granulocytemacrophage colony-stimulating factor (GM-CSF) and insulin. The inhibition of PI3K activity with wortmannin showed that rate of pseudopod extension stimulated with N-formyl-Met-Leu-Phe (fMLP was mostly dependent on PI3K, while the rate of interleukin-8 (IL-8)-stimulated pseudopod extension was less dependent on PI3K. The incubation of cells with either GM-CSF or insulin increased the rate of pseudopod extension by 50% when the cells were stimulated with IL-8 but not with fMLP. The stimulation with IL-8 phosphorylated the PI3K regulatory subunit. This phosphorylation was enhanced by GM-CSF, which increased PI3K activity and total phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P 3 ) production. The effect of GM-CSF was blocked with wortmannin. In contrast, insulin did not increase p85 phosphorylation and did not enhance PI3K activity or PtdIns(3,4,5)P 3 production. The effect of insulin was insensitive to wortmannin; however, it was blocked by an Src homology 2 (SH2) - IntroductionDirectional F-actin polymerization in the lamella region of a migrating human neutrophil is signaled by G-protein-coupled chemotactic receptors (GPCRs). It is known that the ligation of these receptors triggers the release of G ␤␥ . 1 Downstream from the GPCRs, the regulation of F-actin polymerization depends on PI3K activation and PtdIns(3,4,5)P 3 production, and involves the activation of protein kinase B (Akt/PKB) and the guanosine triphosphatases (GTPases) Cdc42 and Rac2. 2,3 Cdc42 and Rac2 form complexes with the Wiskott-Aldrich syndrome protein (WASp) family proteins and actin-related protein 2/3 (Arp2/3) to promote the formation of free barbed ends, 4 which in turn initiate cytoskeletal F-actin polymerization in the lamella region. 3 This mechanism of F-actin polymerization provides a useful framework for the understanding of the signaling of actin dynamics in the living cell during motility; however, it is far from complete. The earlier findings that F-actin polymerization is independent of the release of intracellular calcium and the activation of phospholipase C-␤ suggest that the signaling of migration is distinct from signaling of secretion. [5][6][7] In contrast, there is strong supporting evidence for the dependence of neutrophil migration on the activation of phosphatidylinositol 3-kinase-␥ (PI3K␥) in mice. 6,8,9 Similar dependence on PI3K␥ is expected for the migration of the human neutrophil on the basis of the dramatic change of PI3K␥ activity after neutrophil stimulation with chemoattractant 10 and the ability of the PI3K␥ product, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P 3 ), to induce crawling. 11 However, mouse neutrophils lacking PI3K␥ activity...

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The effect of interleukin-8 and granulocyte macrophage colony stimulating factor on the response of neutrophils to formyl methionyl leucyl phenylalanine

Cited by 9 publications

References 20 publications

Serum and bronchial lavage fluid concentrations of IL-8, SLPI, sCD14 and sICAM-1 in patients with COPD and asthma

Serum and bronchial lavage fluid concentrations of IL-8, SLPI, sCD14 and sICAM-1 in patients with COPD and asthma

Impaired interleukin-8- and GROα-induced phosphorylation of extracellular signal-regulated kinase result in decreased migration of neutrophils from patients with myelodysplasia

Novel pathways of F-actin polymerization in the human neutrophil

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