Aging-Impaired Filamentous Actin Polymerization Signaling Reduces Alveolar Macrophage Phagocytosis of Bacteria

Li, Zhigang; Jiao, Yang; Fan, Erica K.; Scott, Melanie J.; Li, Yuehua; Li, Song; Billiar, Timothy R.; Wilson, Mark A.; Shi, Xueyin; Fan, Jie

doi:10.4049/jimmunol.1700140

Cited by 45 publications

(43 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, our results are in accordance with the report showing the age‐dependently elevated expression of MARCO on the surface of microglia . On the other hand, it was shown that there is no difference in the level of MARCO expression between young and aged alveolar Mф . Importantly, expression of MARCO was significantly up‐regulated in lipopolysaccharide‐induced tolerant Mф .…”

Section: Discussionsupporting

confidence: 92%

Age‐dependent effect between MARCO and TLR4 on PMMA particle phagocytosis by macrophages

Yamada

Beron‐Pelusso

Algazzaz

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Progressive generation of total joint implant‐derived wear particles is one of the major risk factors in development of peri‐prosthetic osteolysis especially in the aging society. It is commonly accepted that macrophages predominantly drive the inflammatory response to wear debris particles. Among various surface receptors that activate the macrophages to phagocytize particles, it is believed that the Toll‐like receptor 4 (TLR4) and the scavenger macrophage receptor with collagenous structure (MARCO) play key roles in recognition of wear debris particles. However, a strong body of evidence indicates an age‐dependent diminished function of human TLRs. Thus, we hypothesized that the MARCO receptor may be more engaged than TLRs in the phagocytosis of wear debris particles which in turn up‐regulate production of pro‐inflammatory cytokines from aged macrophages. We demonstrated that peritoneal macrophages isolated from aged mice show elevated expression of MARCO receptor compared to that from young mice. In contrast the expression of TLR4 was significantly decreased on the surface of aged macrophages. Furthermore, using anti‐MARCO and anti‐TLR4 neutralizing mAbs, we demonstrated the age‐dependent pathogenic role of MARCO, but not TLR4, receptor in promoting poly‐methyl methacrylate (PMMA) bone cement particles phagocytosis by macrophages leading to the release of pro‐inflammatory cytokines migration inhibitory factor and tumour necrosis factor in vitro. These data also suggest that the approach to neutralize MARCO may lead to the development of therapeutic regimen for the prevention of particle‐induced osteolysis in aged patients.

show abstract

Section: Discussionsupporting

confidence: 92%

Age‐dependent effect between MARCO and TLR4 on PMMA particle phagocytosis by macrophages

Yamada

Beron‐Pelusso

Algazzaz

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…Further study is required to determine whether baseline elevations of the receptors we have identified as upregulated on MDMs from COPD subjects, are also increased in alveolar macrophages, though complement receptor 3 (CR3) and CR4 expression on AM have been shown to have higher baseline expression in subjects with COPD (both current and ex-smokers) as compared to non-smoker controls[35, 40, 41]. Whether these receptors will downregulate after bacterial challenge in alveolar macrophages, similarly to the MDMs, is also unknown, particularly for the key scavenger receptors SR-AI and MARCO, though reductions have been observed in murine models[42]. The current data on responses of bacterial recognition receptors on human alveolar macrophages to bacterial exposure in COPD is limited to a single study, where TLR2 and TLR4 increased expression after challenge with live Moraxella catarrhalis (MC), NTHI and SP in adherent alveolar macrophages[26].…”

Section: Discussionmentioning

confidence: 99%

Bacterial regulation of macrophage bacterial recognition receptors in COPD are differentially modified by budesonide and fluticasone propionate

et al. 2019

View full text Add to dashboard Cite

RationalePatients with COPD have an increased risk for community-acquired pneumonia, which is further increased by inhaled corticosteroids.ObjectiveTo assess effects of the corticosteroids, budesonide and fluticasone propionate, on macrophage bacterial responses in COPD.MethodsMonocyte-derived macrophages (MDMs) generated from blood monocytes from 10 non-smoker controls (NoS), 20 smokers without COPD (Sm), and 40 subjects with moderate to severe COPD (21 ex-smokers (COPD-ES) and 19 current smokers (COPD-S)) were pre-treated with budesonide or fluticasone (10 nM—1 μM) and challenged with live non-typeable Haemophilus influenzae (NTHI) or Streptococcus pneumoniae (SP). Cell surface bacterial recognition receptor expression (flow cytometry) and cytokine release (bead array) were analyzed.ResultsNTHI and SP reduced bacterial recognition receptor expression on MDMs from COPD and Sm, but not NoS (except TLR4). SR-AI and MARCO were reduced by both NTHI and SP, whereas other receptors by either NTHI or SP. Among COPD subjects, COPD-ES demonstrated a greater number of reductions as compared to COPD-S. NTHI reduced SR-AI, MARCO, CD11b, CD35 and CD206 in COPD-ES while only SR-AI and CD11b in COPD-S. SP reduced SRA-1, CD1d, TLR2 and TLR4 in both COPD-ES and COPD-S, and reduced MARCO and CD93 only in COPD-ES. All receptors reduced in COPD by NTHI and most by SP, were also reduced in Sm. Budesonide counteracted the receptor reductions induced by both NTHI (CD206 p = 0.03, MARCO p = 0.08) and SP (SR-AI p = 0.02) in COPD-ES. Fluticasone counteracted only SP-induced reductions in TLR2 (p = 0.008 COPD-ES and p = 0.04 COPD-S) and TLR4 (p = 0.02 COPD-ES). Cytokine release was equivalently reduced by both corticosteroids.ConclusionsReduction in macrophage bacterial recognition receptors during bacterial exposure could provide a mechanism for the increased pneumonia risk in COPD. Differential effects of budesonide and fluticasone propionate on macrophage bacterial recognition receptor expression may contribute to the higher pneumonia incidence reported with fluticasone propionate.

show abstract

“…This increased ROS production in ADMSCs from aged rats was attenuated by CASIN with no significant effects on CM-H2DCFDA intensity in younger cells. Impaired actin polymerization is another hallmark of cell senescence (Kasper et al 2009;Li et al 2017;Xu et al 2017), and it can be mediated by the upregulation and activation of Cdc42 (Tang and Gunst 2004;Zlotorynski 2015). We employed QIM of F-actin labeled with Actin-green TM 488 ReadyProbes TM cells to quantify actin polymerization in ADMSCs isolated from young and old animals.…”

Section: Admscs From Young and Aged Ratsmentioning

confidence: 99%

Elevated levels of the small GTPase Cdc42 induces senescence in male rat mesenchymal stem cells

et al. 2018

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) represent a promising cell source for cellular therapy and tissue engineering and are currently being tested in a number of clinical trials for various diseases. However, like other somatic cells, MSCs age, and this senescence is accompanied by a progressive decline in stem cell function. Several lines of evidence suggest a role for the Rho family GTPase Cdc42 activity in cellular senescence processes. In the present study, we have examined aging-associated Cdc42 activity in rat adipose-derived mesenchymal stem cells (ADMSCs) and the consequences of pharmacological inhibition of Cdc42 in ADMSCs from aged rats. We demonstrate that ADMSCs show a decreased rate of cell growth and a decreased ability to differentiate into chrodrogenic, osteogenic and adipogenic cell lineages as a function of rat age. This is accompanied with an increased staining for SA-β-Gal activity and increased levels of Cdc42 bound to GTP. Treatment of ADMSCs from 24-month old rats with three Cdc42 inhibitors significantly increased proliferation rates, decreased SA-β-Gal staining, and reduced Cdc42-GTP. The Cdc42 inhibitor CASIN increased adipogenic and osteogenic differentiation potential in ADMSCs from 24-month old rats, and decreased the levels of radical oxygen species (ROS), p16 levels, F-actin, and the activity of the ERK1/2 and JNK signaling pathways that were all elevated in these cells. These data suggest that ADMSCs show increased rates of senescence as rats age that appear to be due to elevated Cdc42 activity. Thus, Cdc42 plays important roles in MSC senescence and differentiation potential, and pharmacological reduction of Cdc42 activity can, at least partially, rejuvenate aged MSCs.

show abstract

Aging-Impaired Filamentous Actin Polymerization Signaling Reduces Alveolar Macrophage Phagocytosis of Bacteria

Cited by 45 publications

References 48 publications

Age‐dependent effect between MARCO and TLR4 on PMMA particle phagocytosis by macrophages

Age‐dependent effect between MARCO and TLR4 on PMMA particle phagocytosis by macrophages

Bacterial regulation of macrophage bacterial recognition receptors in COPD are differentially modified by budesonide and fluticasone propionate

Elevated levels of the small GTPase Cdc42 induces senescence in male rat mesenchymal stem cells

Contact Info

Product

Resources

About