Inhibition of Human Neutrophil Apoptosis byParacoccidioides brasiliensis: Role of Interleukin-8

LPS and mitogen-stimulated mononuclear cells secrete a cytokine, which is able to activate the PMNL-arachidonate-5-lipoxygenase. This cytokine has been proven to be identical with the recently characterized novel neutrophil-activating peptide NAP/IL-8. NAP/IL-8 is able to activate human PMNL for release of LTB4, omega-oxidized LTB4, and 5-HETE in the presence of exogenous AA. Half-maximal concentration of NAP/IL-8 for release of LTB4 has been found to be near 4 x 10(-8) mol/liter. Time course studies revealed rapid activation of PMNL, with maximal release of LTB4 within the first 10 min with a decline up to 40 min. High amounts of omega-oxidized LTB4 were detected up to that time. Significant amounts of AA-5-LO-products can be detected only when PMNL were stimulated with NAP/IL-8 in the presence of exogenous AA. The concentration of AA necessary for half-maximal LTB4 release has been found to be 3 x 10(-6) mol/liter. In the presence of 8 x 10(-9) mol/liter [3H]AA, NAP/IL-8 (10(-9) to 10(-7) mol/liter) did not induce the production of LTB4, omega-oxidized LTB4, or 5-HETE. In addition, PMNL prelabeled with [3H]AA did not release either [3H]AA or 5-lipoxygenase metabolites when stimulated with NAP/IL-8 (10(-9) to 10(-7) mol/liter), indicating that NAP/IL-8 apparently does not activate cellular phospholipases/diacylglycerol-lipases. Apart from FMLP, C5a, and PAF NAP/IL-8 is the fourth clearly characterized neutrophil chemotaxin able to activate the PMNL-5-lipoxygenase. The detection of large amounts of NAP/IL-8, arachidonic acid, as well as LTB4-like material, in lesional material of patients with psoriasis points towards a possibly important role of NAP/IL-8 in amplifying inflammatory processes by induction of LTB4-production.

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The role of the MAPK pathway alterations in GM-CSF modulated human neutrophil apoptosis with aging

Immunity & Ageing ◽

10.1186/1742-4933-2-6 ◽

2005 ◽

Vol 2 (1) ◽

Cited By ~ 57

Author(s):

Anis Larbi ◽

Nadine Douziech ◽

Carl Fortin ◽

Annie Linteau ◽

Gilles Dupuis ◽

...

Keyword(s):

Human Neutrophil ◽

Mapk Pathway ◽

Neutrophil Apoptosis ◽

Gm Csf

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Flow Cytometric Evaluation of Human Neutrophil Apoptosis During Nitric Oxide Generation In Vitro: The Role of Exogenous Antioxidants

Mediators of Inflammation ◽

10.1155/mi.2005.81 ◽

2005 ◽

Vol 2005 (2) ◽

pp. 81-87 ◽

Cited By ~ 13

Author(s):

Zofia Sulowska ◽

Ewa Majewska ◽

Magdalena Klink ◽

Malgorzata Banasik ◽

Henryk Tchórzewski

Keyword(s):

Nitric Oxide ◽

Human Neutrophil ◽

Flow Cytometric Analysis ◽

Human Neutrophils ◽

Neutrophil Apoptosis ◽

No Donor ◽

No Donors ◽

Flow Cytometric

Among numerous inflammatory mediators a nitric oxide molecule is supposed to be important in the modulation of neutrophil survival in vivo and in vitro. The effect of exogenous supply of NO donors such as SNP, SIN-1, and GEA-3162 on the course of human neutrophil apoptosis and the role of extracellular antioxidants in this process was investigated. Isolated from peripheral blood, neutrophils were cultured in the presence or absence of NO donor compounds and antioxidants for 8, 12, and20hours. Apoptosis of neutrophils was determined in vitro by flow cytometric analysis of cellular DNA content and Annexin V protein binding to the cell surface. Exposure of human neutrophils to GEA-3162 and SIN-1 significantly accelerates and enhances their apoptosis in vitro in a time-dependent fashion. In the presence of SNP, intensification of apoptosis has not been revealed until12hours after the culture. The inhibition of GEA-3162- and SIN-1-mediated neutrophil apoptosis by superoxide dismutase (SOD) but not by catalase (CAT) was observed. Our results show that SOD and CAT can protect neutrophils against NO-donors-induced apoptosis and suggest that the interaction of NO and oxygen metabolites signals may determine the destructive or protective role of NO donor compounds during apoptotic neutrophil death.

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