Sphingosine 1-phosphate antagonizes human neutrophil apoptosis via p38 mitogen-activated protein kinase.

• Sphingosine 1-phosphate (SPP) is associated with the regulation of apoptosis, although its role in neutrophil apoptosis remains poorly investigated. Here, we show that exogenous SPP antagonizes spontaneous and anti-Fas-induced apoptosis in neutrophils. Pre-treatment with pertussis toxin clearly reduced the apoptosis-inhibiting capacity of SPP. Consequently, we investigated the involvement of potential modulators of apoptosis that are activated downstream of Gi/G0-coupled receptors. Neither Akt activity nor change in basal activity of c-Jun N-terminal kinases was detected during apoptosis or after adding SPP. In contrast, there was a transient decrease in phosphorylation of both extracellular-regulated kinase (ERK) and p38mitogen-activated protein kinase (MAPK) during both spontaneous and anti-Fas-induced apoptosis. Although exogenous SPP reversed these reductions in kinase activity, experiments with inhibitors of ERK (PD98059) and p38 MAPK (SB203580) revealed that only SB203580 counteracted the effect of SPP. Thus, SPP counteracts neutrophil apoptosis via a Gi/G0protein survival-signalling pathway that includes modulation of p38 MAPK activity.

Subject headings

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

Keyword

Neutrophils: physiology

Apoptosis: drug effects

Apoptosis: physiology

Enzyme Inhibitors: pharmacology

Flavones: pharmacology

Human

Imidazoles: pharmacology

Mitogen-Activated Protein Kinases: antagonists & inhibitors

Mitogen-Activated Protein Kinases: metabolism

Phosphorylation

Pyridines: pharmacology

Signal Transduction: physiology

Sphingosine: analogs & derivatives

Sphingosine: metabolism

Support

Non-U.S. Gov't

Publication and Content Type

art (subject category)

ref (subject category)