scholarly journals Poly-d-lysine coated nanoparticles to identify pro-inflammatory macrophages

2020 ◽  
Vol 2 (9) ◽  
pp. 3849-3857
Author(s):  
Derek S. Hernandez ◽  
Hattie C. Schunk ◽  
Karan M. Shankar ◽  
Adrianne M. Rosales ◽  
Laura J. Suggs
Keyword(s):  
Real Time ◽  
Fluorescent Labeling ◽  
M1 Macrophages ◽  
Coated Nanoparticles ◽  
Inflammatory Macrophages ◽  
Coated Nanoparticle ◽  
Diagnose Monitor

Identifying pro-inflammatory macrophages (M1) is of immense importance to diagnose, monitor, and treat various pathologies. Here, we present a poly-D-lysine coated nanoparticle for real-time fluorescent labeling of M1 macrophages.

scholarly journals Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2

2020 ◽  
Author(s):  
Fuyu Duan ◽  
Liyan Guo ◽  
Liuliu Yang ◽  
Yuling Han ◽  
Abhimanyu Thakur ◽  
...  
Keyword(s):  
Early Stage ◽  
Synergistic Effects ◽  
Inflammatory Factors ◽  
Target Cells ◽  
Lung Cells ◽  
Alveolar Type ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Anti Inflammatory ◽  
Inflammatory Macrophages

Abstract Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies. Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection. Among the hPSC-derived lung cells, alveolar type II and ciliated cells are the major cell populations expressing the viral receptor ACE2 and co-effector TMPRSS2, and both were highly permissive to viral infection. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 and IL-18, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper-inflammatory response mediated by M1 macrophages.

scholarly journals Proteoglycan-4 is an essential regulator of synovial macrophage polarization and inflammatory macrophage joint infiltration

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Marwa Qadri ◽  
Gregory D. Jay ◽  
Ling X. Zhang ◽  
Tannin A. Schmidt ◽  
Jennifer Totonchy ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Membrane Thickness ◽  
Type I ◽  
Surface Markers ◽  
M1 Macrophages ◽  
Synovial Hyperplasia ◽  
Synovial Macrophage ◽  
Proteoglycan 4 ◽  
Inflammatory Macrophages ◽  
The Impact

Abstract Background Synovial macrophages perform a multitude of functions that include clearance of cell debris and foreign bodies, tissue immune surveillance, and resolution of inflammation. The functional diversity of macrophages is enabled by distinct subpopulations that express unique surface markers. Proteoglycan-4 (PRG4) is an important regulator of synovial hyperplasia and fibrotic remodeling, and the involvement of macrophages in PRG4’s synovial role is yet to be defined. Our objectives were to study the PRG4’s importance to macrophage homeostatic regulation in the synovium and infiltration of pro-inflammatory macrophages in acute synovitis and investigate whether macrophages mediated synovial fibrosis in Prg4 gene-trap (Prg4GT/GT) murine knee joints. Methods Macrophage phenotyping in Prg4GT/GT and Prg4+/+ joints was performed by flow cytometry using pan-macrophage markers, e.g., CD11b, F4/80, and surface markers of M1 macrophages (CD86) and M2 macrophages (CD206). Characterizations of the various macrophage subpopulations were performed in 2- and 6-month-old animals. The expression of inflammatory markers, IL-6, and iNOS in macrophages that are CD86+ and/or CD206+ was studied. The impact of Prg4 recombination on synovial macrophage populations of 2- and 6-month-old animals and infiltration of pro-inflammatory macrophages in response to a TLR2 agonist challenge was determined. Macrophages were depleted using liposomal clodronate and synovial membrane thickness, and the expression of fibrotic markers α-SMA, PLOD2, and collagen type I (COL-I) was assessed using immunohistochemistry. Results Total macrophages in Prg4GT/GT joints were higher than Prg4+/+ joints (p<0.0001) at 2 and 6 months, and the percentages of CD86+/CD206− and CD86+/CD206+ macrophages increased in Prg4GT/GT joints at 6 months (p<0.0001), whereas the percentage of CD86−/CD206+ macrophages decreased (p<0.001). CD86+/CD206− and CD86+/CD206+ macrophages expressed iNOS and IL-6 compared to CD86−/CD206+ macrophages (p<0.0001). Prg4 re-expression limited the accumulation of CD86+ macrophages (p<0.05) and increased CD86−/CD206+ macrophages (p<0.001) at 6 months. Prg4 recombination attenuated synovial recruitment of pro-inflammatory macrophages in 2-month-old animals (p<0.001). Clodronate-mediated macrophage depletion reduced synovial hyperplasia, α-SMA, PLOD2, and COL-I expressions in the synovium (p<0.0001). Conclusions PRG4 regulates the accumulation and homeostatic balance of macrophages in the synovium. In its absence, the synovium becomes populated with M1 macrophages. Furthermore, macrophages exert an effector role in synovial fibrosis in Prg4GT/GT animals.

Light-responsive amphiphilic copolymer coated nanoparticles as nanocarriers and real-time monitors for controlled drug release

2014 ◽  
Vol 2 (9) ◽  
pp. 1182 ◽  
Author(s):  
Qingjian Xing ◽  
Najun Li ◽  
Dongyun Chen ◽  
Wenwei Sha ◽  
Yang Jiao ◽  
...  
Keyword(s):  
Drug Release ◽  
Real Time ◽  
Controlled Drug Release ◽  
Amphiphilic Copolymer ◽  
Coated Nanoparticles

scholarly journals Metformin Triggers Apoptosis and Induction of the G0/G1 Switch 2 Gene in Macrophages

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1437
Author(s):  
Xuming Hu ◽  
Huan Luo ◽  
Chunfeng Dou ◽  
Xujing Chen ◽  
Yi Huang ◽  
...  
Keyword(s):  
Marker Genes ◽  
M2 Macrophage ◽  
Dependent Manner ◽  
M1 Macrophages ◽  
Inflammatory Mechanism ◽  
Anti Inflammatory ◽  
Induced Apoptosis ◽  
Inflammatory Macrophages ◽  
Dose Dependent

Metformin is a widely used antidiabetic drug for the treatment of type 2 diabetes and has been recently demonstrated to possess anti-inflammatory properties via AMPK-mediated modulation of M2 macrophage activation. However, the anti-inflammatory mechanisms of metformin on inflammatory macrophages are still not fully elucidated. In this study, we found that metformin induced apoptosis in macrophages. In particular, metformin induced apoptosis of M1 macrophages, based on M1 marker genes in apoptotic macrophages. Next, we comprehensively screened metformin-responsive genes in macrophages by RNA-seq and focused on the extrinsic apoptotic signaling pathway. The G0/G1 switch 2 gene (G0S2) was robustly up-regulated by metformin in macrophages. Overexpression of G0S2 significantly induced apoptosis of macrophages in a dose-dependent manner and blunted the function of the crucial anti-apoptotic gene Bcl-2, which was significantly reduced by metformin. These findings show that metformin promoted apoptosis of macrophages, especially M1 macrophages, via G0S2 induction and provides a novel anti-inflammatory mechanism of metformin through induction of macrophage apoptosis.

scholarly journals Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Hao Wang ◽  
Xueyue Zheng ◽  
Bingnan Liu ◽  
Yaoyao Xia ◽  
Zhongquan Xin ◽  
...  
Keyword(s):  
Immune Cells ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Hypoxia Inducible Factor ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ifn Γ ◽  
Inflammatory Macrophages

Increasing evidence support that cellular amino acid metabolism shapes the fate of immune cells; however, whether aspartate metabolism dictates macrophage function is still enigmatic. Here, we found that the metabolites in aspartate metabolism are depleted in lipopolysaccharide (LPS) plus interferon gamma (IFN-γ)-stimulated macrophages. Aspartate promotes interleukin-1β (IL-1β) secretion in M1 macrophages. Mechanistically, aspartate boosts the activation of hypoxia-inducible factor-1α (HIF-1α) and inflammasome and increases the levels of metabolites in aspartate metabolism, such as asparagine. Interestingly, asparagine also accelerates the activation of cellular signaling pathways and promotes the production of inflammatory cytokines from macrophages. Moreover, aspartate supplementation augments the macrophage-mediated inflammatory responses in mice and piglets. These results uncover a previously uncharacterized role for aspartate metabolism in directing M1 macrophage polarization.

scholarly journals Collagen-derived peptide, DGEA, inhibits pro-inflammatory macrophages in biofunctional hydrogels

2021 ◽  
Author(s):  
Aakanksha Jha ◽  
Erika Moore
Keyword(s):  
Macrophage Activation ◽  
Innate Immune ◽  
M1 Macrophages ◽  
Inflammatory Conditions ◽  
M1 Macrophage ◽  
Inflammatory Stimuli ◽  
Poly Ethylene ◽  
Inflammatory Macrophages ◽  
Inflammatory Macrophage

AbstractMacrophages are innate immune cells that play important roles in wound healing. Particularly, M1 macrophages are considered pro‐inflammatory and promote initial phases of inflammation. Long-term exposure to inflammatory stimuli causes an increase in M1 macrophages, which contributes to chronic inflammation. Activated M1 macrophages have been shown to upregulate integrin α2β1 expression. To interfere with α2β1 binding, we designed a biofunctional hydrogel utilizing a collagen I-derived peptide, DGEA (Asp-Gly-Glu-Ala). We hypothesize that M1 macrophage activation can be reduced in the presence of DGEA. Effects of DGEA on M1 macrophages were studied via soluble delivery and immobilization within poly(ethylene glycol) (PEG) hydrogels. We demonstrate that M1 macrophage activation is reduced both via soluble delivery of DGEA in 2D and via immobilized DGEA in a 3D PEG-DGEA hydrogel. This novel biomaterial can manipulate inflammatory macrophage activation and can be applied to prevent chronic inflammatory conditions via macrophage manipulation. Graphical abstract

scholarly journals Migration of endothelial cells into photo-responsive hydrogels with tunable modulus under the presence of pro-inflammatory macrophages

2019 ◽  
Vol 6 (5) ◽  
pp. 259-267 ◽  
Author(s):  
Wangbei Cao ◽  
Xuguang Li ◽  
Xingang Zuo ◽  
Changyou Gao
Keyword(s):  
Endothelial Cells ◽  
Uv Irradiation ◽  
Tissue Regeneration ◽  
Three Dimensional ◽  
Mesh Size ◽  
Model System ◽  
Biological Processes ◽  
M1 Macrophages ◽  
Inflammatory Macrophages ◽  
Responsive Hydrogels

Abstract Cell migration in three-dimensional environment is extremely important for tissue regeneration and other biological processes. In this work, a model system was developed to study how endothelial cells (ECs) migrate into photo-responsive hydrogels under the presence of pro-inflammatory macrophages. The hydrogel was synthesized from hyaluronic acid grafted with coumarin and methacrylate moieties by both carbon–carbon covalent linking and coumarin dimerization under UV irradiation at 365 nm. The structure of the hydrogel was conveniently modulated by UV irradiation at 254 nm to decompose the coumarin dimers, leading to the significant decrease of modulus and increase of swelling ratio and mesh size. Under the presence of M1 macrophages, ECs were induced to migrate into the hydrogels with a different degree. A significant larger net displacement of ECs was found in the softer hydrogel obtained by irradiation with UV at 254 nm than in the stiffer original one at day 7.

scholarly journals CDC-derived extracellular vesicles reprogram inflammatory macrophages to an arginase 1-dependent proangiogenic phenotype

2020 ◽  
Vol 318 (6) ◽  
pp. H1447-H1460 ◽  
Author(s):  
Kyle I. Mentkowski ◽  
Asma Mursleen ◽  
Jonathan D. Snitzer ◽  
Lindsey M. Euscher ◽  
Jennifer K. Lang
Keyword(s):  
Myocardial Infarction ◽  
Extracellular Vesicles ◽  
Macrophage Polarization ◽  
Extracellular Vesicle ◽  
Primary Target ◽  
Relevant Model ◽  
M1 Macrophages ◽  
Arginase 1 ◽  
Inflammatory Macrophages ◽  
Insight Into

We hypothesized that in the window of therapeutic extracellular vesicle (EV) administration, inflammatory M1 macrophages are likely the primary target of cardiosphere-derived cell (CDC)-derived EVs. The effect of CDC-EVs on this population, however, is currently unknown. In this study, we demonstrate that CDC-derived EVs polarize M1 macrophages to a proangiogenic phenotype dependent on arginase 1 upregulation. These results provide insight into an immunomodulatory mechanism of CDC-EVs in a more physiologically relevant model of post-myocardial infarction (post-MI) macrophage polarization.

scholarly journals A real-time monitoring platform of myogenesis regulators using double fluorescent labeling

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192654 ◽  
Author(s):  
Etai Sapoznik ◽  
Guoguang Niu ◽  
Yu Zhou ◽  
Peter M. Prim ◽  
Tracy L. Criswell ◽  
...  
Keyword(s):  
Real Time ◽  
Fluorescent Labeling ◽  
Real Time Monitoring ◽  
Monitoring Platform
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