Aging impairs peritoneal but not bone marrow‐derived macrophage phagocytosis

Linehan, Eimear; Dombrowski, Yvonne; Snoddy, Rachel; Fallon, Padraic G.; Kissenpfennig, Adrien; Fitzgerald, Denise

doi:10.1111/acel.12223

Cited by 134 publications

(128 citation statements)

References 41 publications

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“…We demonstrated that this impairment was due to age-related changes in the microenvironment in the peritoneum and not intrinsic defects in macrophages. As such, we suggest that defects may be reversible and macrophages could be targeted therapeutically in order to boost immune function in the elderly [96]. One potential area of controversy in murine studies is the age of young and old mice.…”

Section: Macrophage Phagocytosismentioning

confidence: 97%

Ageing and the immune system: focus on macrophages

Linehan¹,

Fitzgerald²

2015

European Journal of Microbiology and Immunology

176

136

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A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population.

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Section: Macrophage Phagocytosismentioning

confidence: 97%

Ageing and the immune system: focus on macrophages

Linehan¹,

Fitzgerald²

2015

European Journal of Microbiology and Immunology

176

136

View full text Add to dashboard Cite

show abstract

“…Studies on peripheral immunity have shown a loss of phagocytic capacity and function in macrophages with age (Plowden et al 2004), although this result is not consistent across all studies (Gardner et al 1981) and may differ between inflammatory cell types (Linehan et al 2014). Cultured macrophages from aged humans have a diminished phagocytic capacity for myelin debris (Natrajan et al 2015), and in vivo studies have shown that the rate of remyelination is reduced in aged rodents but can be restored with an infusion of monocytes from young animals (Ruckh et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey

et al. 2017

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While cognitive decline is observed in the normal aging monkey, neurons are not lost with age. Instead, frontal white matter is lost as myelin degenerates and both correlate with age-related cognitive decline. As age-related myelin damage increases, there should be an increase in clearance of damaged myelin by microglial phagocytosis. In this study, brains of behaviorally tested rhesus monkeys were assessed using unbiased stereology to quantify the density of activated microglia (LN3 antibody positive) and phagocytic microglia (galectin-3 (Gal-3) antibody positive) in three white matter regions: the corpus callosum, cingulum bundle (CGB), and frontal white matter (FWM). LN3 cell density was significantly increased in the CGB, whereas Gal-3 cell density was significantly increased in all regions. Increases in Gal-3 cell density in the FWM were associated with cognitive impairment. In the FWM of old animals, Gal-3-positive microglia were classified by morphological subtype as ramified, hypertrophic, or amoeboid. The densities of hypertrophic and amoeboid microglia significantly correlated with cognitive impairment. Finally, microglia were double-labeled with LN3 and Gal-3 showing that 91% of Gal-3 cells were also LN3 positive, thus expressing an Bactivated^phenotype. Furthermore, 15% of all double-labeled cells formed phagocytic cups. Overall, these results suggest that microglia become activated in white matter with age where the majority express a phagocytic phenotype. We hypothesize that age-related phagocytic activation of microglia is a response to accumulating myelin pathology. The association of Gal-3 in the FWM with cognitive impairment may reflect regional differences in damage or dysfunction of normal clearance mechanisms.

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“…The mechanisms of sepsis-induced heart failure have been rised concerns both in basic and clinic research. An ample of molecular mechanisms such as apoptosis, immune regulation, mitochondria, and energy metabolism have been revealed [11–13]. Autophagy is associated with accelerated cardiac aging.…”

Section: Introductionmentioning

confidence: 99%

The endotoxemia cardiac dysfunction is attenuated by AMPK/mTOR signaling pathway regulating autophagy

Zhang

Zhao

Quan

et al. 2017

Biochemical and Biophysical Research Communications

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AMP-activated protein kinase (AMPK), an enzyme that plays a role in cellular energy homeostasis, modulates myocardial signaling in the heart. Myocardial dysfunction is a common complication of sepsis. Autophagy is involved in the aging related cardiac dysfunction. However, the role of AMPK in sepsis-induced cardiotoxicity has yet to be clarified, especially in aging. In this study, we explored the role of AMPK in lipopolysaccharide (LPS)-induced myocardial dysfunction and elucidated the potential mechanisms of AMPK/mTOR pathway regulating autophagy in young and aged mice. We harvested cardiac tissues by intraperitoneal injection of LPS treatment. The results by echocardiography, pathology, contractile and intracellular Ca2+ property as well as western blot analysis revealed that LPS induced remarkable cardiac dysfunction and cardiotoxicity in mice hearts and cardiomyocytes, which were more seriously in the aged mice. Western blot analysis indicated that the underlying mechanisms included inhibition autophagy mediated by AMPK/mTOR activation. LPS overtly promoted the expression of AMPK upstream regulator PP2A and PP2Cα. Pharmacological activation of AMPK improved cardiac function and upregulated cardiac autophagy induced by LPS in the aged mice. Collectively, our findings suggest that upregulation of autophagy by administration of AMPK could attenuate LPS-induced cardiotoxicity, which enhances our knowledge to explore new drugs and strategies for combating cardiac dysfunction induced by sepsis.

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Aging impairs peritoneal but not bone marrow‐derived macrophage phagocytosis

Cited by 134 publications

References 41 publications

Ageing and the immune system: focus on macrophages

Ageing and the immune system: focus on macrophages

Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey

The endotoxemia cardiac dysfunction is attenuated by AMPK/mTOR signaling pathway regulating autophagy

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