Age-dependent alterations of human recombinant GM-CSF effects on human granulocytes

Serés, I.; Csongor, J.; Mohácsi, Attila; Leövey, A; Fülöp, Tamás

doi:10.1016/0047-6374(93)90042-p

Cited by 34 publications

(14 citation statements)

References 33 publications

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“…A recent review has shown that actin polymerisation, calcium mobilisation and GM-CSF production are all reduced in healthy elderly patients, compared to younger controls [22]. Furthermore, neutrophils from elderly subjects are not primed as efficiently by GM-CSF as those from normal controls [23]. This would suggest that elderly patients with coronary artery disease should be less likely to have neutrophil shape changes than younger controls.…”

Section: Discussionmentioning

confidence: 96%

Automated quantitation of peripheral blood neutrophil activation in patients with myocardial ischaemia

Leckie

Gomma

Purcell

et al. 2004

International Journal of Cardiology

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Section: Discussionmentioning

confidence: 96%

Automated quantitation of peripheral blood neutrophil activation in patients with myocardial ischaemia

Leckie

Gomma

Purcell

et al. 2004

International Journal of Cardiology

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“…The PMN and receptor-driven functions have been demonstrated to be altered with aging [12,[27][28][29][30][31][32][33][34][35][36]. The alterations of the signal transduction manifested by altered tyrosine kinase phosphorylation during various PMN receptor stimulation including GM-CSF and fMLP could partly explain this impairment with aging.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the PMN signal transduction is also altered with aging [27][28][29][30][31][32][33][34][35][36], and over the past few years, it has been demonstrated that these PMN-specific, receptor-driven functions are altered with aging [12,27,32]. The importance of negative regulators of PMN receptors, such as the GM-CSF receptor, in the alteration of the PMN functions has not yet been studied extensively.…”

Section: Introductionmentioning

confidence: 99%

Impairment of SHP-1 down-regulation in the lipid rafts of human neutrophils under GM-CSF stimulation contributes to their age-related, altered functions

Fortin¹,

Larbi²,

Lesur³

et al. 2006

Journal of Leukocyte Biology

104

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It has been shown that the functions and the rescue from apoptosis by proinflammatory mediators of polymorphonuclear leukocytes (PMN) tend to diminish with aging. Here, we investigated the role of protein tyrosine phosphatases (PTP), especially Src homology domain-containing protein tyrosine phosphatase-1 (SHP-1), in the age-related, altered PMN functions under granulocyte macrophage-colony stimulating factor (GM-CSF) stimulation. The inhibition of PTP suggested a differential effect of GM-CSF on phosphatase activity in modulating PMN functions with aging. The down-regulation of phosphatase activity of immunopurified SHP-1 from lipid rafts of PMN of young donors was found significantly altered at 1 min of stimulation with aging. In young donors, SHP-1 is displaced from lipid rafts at 1 min of stimulation, whereas in the elderly, SHP-1 is constantly present. We assessed in PMN lipid rafts the phosphorylation of tyrosine and serine residues of SHP-1, which regulates its activity. We observed an alteration in the phosphorylation of tyrosine and serine residues of SHP-1 in PMN of elderly subjects, suggesting that GM-CSF was unable to inhibit SHP-1 activity by serine phosphorylation. GM-CSF activates Lyn rapidly, and we found alterations in its activation and translocation to the lipid rafts with aging. We also demonstrate that SHP-1 in the PMN of elderly is constantly recruited to Lyn, which cannot be relieved by GM-CSF. In contrast, in the young, the resting recruitment could be relieved by GM-CSF. Our results suggest an alteration of the SHP-1 modulation by GM-CSF in lipid rafts of PMN with aging. These alterations could contribute to the decreased GM-CSF effects on PMN.

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“…Further, pathological mechanisms that accompany imbalance of reactive oxygen intermediates appear to have a larger impact on regulatory mechanisms within networks, more during advancing age than in young cohorts. In innate immune cells, this oxidative stress=imbalance can be observed as altered phagocytic capacity, due to altered intracellular signaling pathways, which impact pathogen killing capacity (111,248,340). Additionally, alterations in cell adhesion cascades and defective ROS metabolism appear to affect further the functional capacity of the cell during aging (51).…”

Section: B Ros Aging and Immune Dysfunctionmentioning

confidence: 99%

Aging and Immune Function: Molecular Mechanisms to Interventions

Ponnappan

2011

Antioxidants & Redox Signaling

290

266

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The immune system of an organism is an essential component of the defense mechanism aimed at combating pathogenic stress. Age-associated immune dysfunction, also dubbed ''immune senescence,'' manifests as increased susceptibility to infections, increased onset and progression of autoimmune diseases, and onset of neoplasia. Over the years, extensive research has generated consensus in terms of the phenotypic and functional defects within the immune system in various organisms, including humans. Indeed, age-associated alterations such as thymic involution, T cell repertoire skewing, decreased ability to activate naïve T cells and to generate robust memory responses, have been shown to have a causative role in immune decline. Further, understanding the molecular mechanisms underlying the generation of proteotoxic stress, DNA damage response, modulation of ubiquitin proteasome pathway, and regulation of transcription factor NFkB activation, in immune decline, have paved the way to delineating signaling pathways that cross-talk and impact immune senescence. Given the role of the immune system in combating infections, its effectiveness with age may well be a marker of health and a predictor of longevity. It is therefore believed that a better understanding of the mechanisms underlying immune senescence will lead to an effective interventional strategy aimed at improving the health span of individuals. Antioxid. Redox Signal. 14, 1551-1585.

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Age-dependent alterations of human recombinant GM-CSF effects on human granulocytes

Cited by 34 publications

References 33 publications

Automated quantitation of peripheral blood neutrophil activation in patients with myocardial ischaemia

Automated quantitation of peripheral blood neutrophil activation in patients with myocardial ischaemia

Impairment of SHP-1 down-regulation in the lipid rafts of human neutrophils under GM-CSF stimulation contributes to their age-related, altered functions

Aging and Immune Function: Molecular Mechanisms to Interventions

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