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Age-related effects of oxidative metabolism and cyclic AMP signaling on neutrophil apoptosis
- Source :
- Mechanisms of ageing and development. 110(3)
- Publication Year :
- 1999
-
Abstract
- Spontaneous as well as Fas-induced polymorphonuclear cell apoptosis is unchanged in the elderly. However, a weak responsiveness to antiapoptotic signals elicited by proinflammatory molecules has been reported in neutrophils isolated from aged humans. To gain insight into this field, here we have evaluated the role of oxidative metabolism and cyclic AMP (cAMP) signaling on age-related neutrophil apoptotic cell death. Results show that although superoxide dismutase (SOD), added exogenously to cell cultures, is able to prolong neutrophil survival in both young and aged individuals, high amounts of the enzyme are further effective in cell cultures of young donors only. Notably, the addition of catalase gives rise to a more striking, yet comparable, inhibition of neutrophil-programmed cell death in both groups of subjects. Furthermore, even low amounts of catalase are enough to restore a normal apoptotic outcome in SOD-treated cell cultures of old donors. Unlike the oxidative metabolism, cAMP signaling activation does not reveal any difference in the apoptotic response of neutrophils isolated from young and aged donors. Thus, supplementation of cell cultures with prostaglandin E2, dibutyryl cAMP or, to a lesser degree, forskolin results in a dose-dependent inhibition of DNA cleavage product appearance in both groups of subjects. The data outline that an impairment of neutrophil antioxidant shield, leading to an augmented cell oxidative load, is likely to occur as a feature of age. This may increase the apoptotic rate of stimulated cells, which may in turn account for the increased susceptibility of elderly individuals to life-threatening infections.
- Subjects :
- Adult
Male
Programmed cell death
medicine.medical_specialty
Aging
Neutrophils
Cell
Apoptosis
Biology
In Vitro Techniques
Antioxidants
Dinoprostone
Proinflammatory cytokine
Superoxide dismutase
chemistry.chemical_compound
Internal medicine
medicine
Cyclic AMP
Humans
Aged
Aged, 80 and over
Forskolin
Superoxide Dismutase
Colforsin
Endocrinology
medicine.anatomical_structure
chemistry
Bucladesine
Cell culture
biology.protein
Female
Signal transduction
Reactive Oxygen Species
Oxidation-Reduction
Developmental Biology
Signal Transduction
Subjects
Details
- ISSN :
- 00476374
- Volume :
- 110
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Mechanisms of ageing and development
- Accession number :
- edsair.doi.dedup.....931573ea0f124fe671c8544c45531788