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Modulation of cytoskeleton assembly capacity and oxidative response in aged neutrophils
G Piazzolla1, C Tortorella, M Serrone
1Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari Medical School, Italy.
Abstract:
Several reports have emphasized that aged polymorphonuclear cells (PMN) exhibit an impairment of superoxide anion (O2-) generation when triggered with formyl-methionyl-leucine-phenylalanine (FMLP) in comparison to the younger counterpart. Since microfilaments and microtubules are involved in PMN-mediated functions, in a group of old donors we assessed the effects of either actin stabilizing and disrupting agents, i.e. phalloidin and cytochalasin B, or microtubule stabilization or disruption by taxol and colchicine, respectively, on FMLP-triggered neutrophil oxidative responsiveness. Results show that phalloidin treatment, at a concentration ranging from 10(-6) to 10(-8) M, gave rise to an inhibition of O2- release by aged PMN, while the same effect was seen in similarly treated young cells at a concentration of 10(-7) M only. On the contrary, cytochalasin B pretreatment led to an enhancement of O2- generation in both young and aged neutrophils, even if to a lower extent in the latter group. At the same time, taxol at 10(-8) M strength inhibited young cell responsiveness, while no effects were induced by colchicine treatment. Quite interestingly, elderly neutrophil function was negatively modulated by both microtubule affecting compounds. Altogether, these findings suggest the possible relevance of cytoskeletal affecting compounds in the modulation of FMLP-stimulated O2- release during senescence.
Insights
Aging impairs neutrophil superoxide anion generation. Cytoskeletal agents like phalloidin and taxol differentially affect this function in aged neutrophils, suggesting potential therapeutic targets for immune senescence.
Area of Science:
- Immunology
- Cell Biology
- Gerontology
Background:
- Aged neutrophils (polymorphonuclear cells, PMN) show reduced superoxide anion (O2-) generation upon stimulation.
- Cytoskeletal components, microfilaments and microtubules, are crucial for PMN functions.
Purpose of the Study:
- To investigate the impact of actin and microtubule modulating agents on FMLP-triggered superoxide generation in aged versus young neutrophils.
- To explore the role of the cytoskeleton in age-related neutrophil dysfunction.
Main Methods:
- Neutrophils from young and old donors were pretreated with actin agents (phalloidin, cytochalasin B) or microtubule agents (taxol, colchicine).
- Superoxide anion (O2-) generation was measured after stimulation with formyl-methionyl-leucine-phenylalanine (FMLP).
Main Results:
- Phalloidin inhibited O2- release in aged PMN at lower concentrations than in young PMN.
- Cytochalasin B enhanced O2- generation in both age groups, but less effectively in aged cells.
- Taxol inhibited young neutrophil responsiveness, while both taxol and colchicine negatively affected aged neutrophil function.
Conclusions:
- Cytoskeletal dynamics play a significant role in the age-related decline of neutrophil oxidative burst.
- Specific cytoskeletal-affecting compounds may differentially modulate neutrophil function during senescence.
- These findings highlight the potential of targeting the cytoskeleton to address immune senescence.