Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets

Abstract Monocyte/macrophage targeting drug delivery system (MTDS) has been highly focused as an emerging routine for delivering drugs to various macrophage related diseases. However, the distinguishing ability towards different macrophage related diseases of these systems and the impact of them on macrophage function and disease progression have not been systematically revealed, which is significantly important for active targeting therapeutic or diagnostic strategies. Herein, taking dextran modified polystyrene nanoparticles (DEX-PS) as example, we demonstrate that modification by dextran can specifically enhance the recognition of nanoparticles (NPs) by M2 macrophages in vitro, however, which is obstructed by monocytes in peripheral blood proved by in vivo assays. DEX-PS is not only targeted distributed in tumor, a M2 macrophage related disease, but also highly distributed in M1 macrophages related disease, acute peritonitis. Additionally, DEX-PS play a double-edged role in these two different diseases by reeducating macrophages to pro-inflammatory phenotype. These results suggest that MTDS, even those designed based on the different expression of receptor on different macrophages subtypes, lacks distinguishing ability for different macrophage subsets related diseases in vivo. In addition to the potential impact of these carrier materials on the function of macrophages, in the study of MTDS, great attention should be paid to the distribution of nanoparticles in non-target diseases and the impact on its disease process.

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Abstract 296: Targeting Macrophage Subsets Attenuates Cardiac Remodeling and Dysfunction Following Experimental Myocarditis in Rat

Circulation Research ◽

10.1161/res.113.suppl_1.a296 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Shunit Rinkevich-Shop ◽

Tamar Ben-Mordechai ◽

David Kain ◽

Micha S. Feinberg ◽

Natalie Landa-Rouben ◽

...

Keyword(s):

Cardiac Remodeling ◽

M2 Macrophage ◽

M2 Macrophages ◽

Autoimmune Myocarditis ◽

Intravenous Injections ◽

Macrophage Depletion ◽

Monocytes And Macrophages ◽

Adverse Remodeling ◽

And Function ◽

Macrophage Subsets

Introduction: The mechanism of myocarditis is complex and poorly understood. Monocytes and macrophages comprise the majority of infiltrates in myocarditis. Hypothesis: We aimed to test the hypothesis that macrophage subsets have a key role in the pathogenesis and progression of myocarditis, and that targeting macrophages would modulate disease progression and outcome. Methods and Results: Experimental autoimmune myocarditis (EAM) was induced in 67 male Lewis rats. Of them, 27 were sacrificed at different time points to assess M1 and M2- macrophage subsets by flow cytometry. The remaining rats were randomized either to early macrophage depletion (from day 8-14 after EAM induction), by intravenous injections of clodronate-liposomes (CL), or late depletion (from day 15-35 after induction of EAM), or PBS-liposome injections (control). Left ventricula (LV) remodeling and function were assessed by echocardiography; before induction of EAM, before CL treatment, and 35 days after induction of EAM. Macrophages in the heart peaked at 21 days after induction of EAM (25±7%,p=0.0008).The number of M1 macrophages in the heart was highest at 14 days after EAM induction (16.3±2%), while M2 macrophages peaked at day 21 (15.5±2.7%,p=0.003). Early macrophage depletion (8-14d) decreased LV diastolic dimension and volume by 5.3±3.9% and 10.4±8% (p=0.04). Late macrophage depletion (15-35d) increased LV wall thickness and decreased LV systolic dimension and volume by 10.2±4% and 21±8% (p=0.03). Furthermore, late macrophage depletion increased LV ejection fraction and fractional shortening by 14.6±6% (p=0.01) and 22±10% (p=0.02) 35 days after EAM. Conclusions: Our study describes, for the first time, the kinetics of M1 and M2 macrophages in ocarditis and shows that macrophages contribute to the progression of adverse remodeling and dysfunction. Thus, targeting macrophages could be a new therapeutic strategy to improve cardiac remodeling and function in myocarditis.

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The Role of M2 Macrophage in Primary Immune Thrombocytopenia

Blood ◽

10.1182/blood-2019-129667 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2355-2355

Author(s):

Xia Shao ◽

Boting Wu ◽

Pu Chen ◽

Yanxia Zhan ◽

Feng Li ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Magnetic Bead ◽

Ppar Gamma ◽

M2 Macrophage ◽

Healthy Controls ◽

M2 Macrophages ◽

Protein Levels ◽

Primary Immune Thrombocytopenia ◽

Macrophage Subsets

Background: Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disorder, characterized by immune-mediated platelet destruction and impaired megakaryocyte maturation. Although impaired T cells have been implicated to participate in the pathogenesis of ITP, another immune cell signified as M2 macrophages has not been investigated properly in ITP patients. This study aimed to investigate the role of M2 macrophage subsets in primary immune thrombocytopenia (ITP). Methods: Peripheral blood mononuclear cells (PBMC) from newly diagnosed ITP patients and healthy controls (HC) were isolated. M2-like macrophages (CD68+CD163+) and M2 macrophages (CX3CR1+CD163+) were measured by flow cytometry. The correlation between CD68+CD163+ cells and CX3CR1+CD163+ cells was also analyzed. The CX3CR1+cells were sorted by magnetic bead, CD68+CD163+ in PBMC of ITP patients and healthy controls were then isolated, and the proportion of m2-like macrophages before and after the sorting was analyzed. The PPAR gamma and arg-1 levels of mRNAs and proteins of CX3CR1+ M2 macrophages were examined by Real-time PCR and Western Blot, respectively. Results: CX3CR1+CD163+M2 macrophages were positively correlated with CD68+ CD163+ M2-like macrophages in ITP patients (r = 0.54, p < 0.01). After magnetic bead separation, the proportion of CD68+CD163+ cells in CX3CR1+ cells was significantly increased (p = 0.02). Compared with HC, both the mRNA and protein levels of arg-1 of CX3CR1+ M2 macrophages were significantly increased in patients with ITP. The expression level of PPAR gamma protein was significantly increased in ITP than that of HC. However no statistical difference was detected at mRNA expression level, although it was numerically higher in ITP patients than in HC ( p = 0.19). Conclusion: The peripheral CX3CR1+ M2 macrophage exercises similar phenotypes and functions of M2 macrophage. The remarkably increased expression of arg-1 at both transcription and protein levels and PPAR gamma at protein level of CX3CR1+M2 macrophages in ITP patients suggests potential immunomodulatory functions of these macrophage subsets during ITP pathogenesis. However, no significant change at mRNA level of PPAR gamma indicating that the increased PPAR gamma protein level might be caused by other mechanisms, such as after transcription abnormalities, which warrants further investigation. Disclosures No relevant conflicts of interest to declare.

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Hypoxia-preconditioned mesenchymal stem cells mitigate renal ischemia-reperfusion injury by modulating M2 macrophage subsets and suppressing oxidative stress

Cytotherapy ◽

10.1016/j.jcyt.2018.02.148 ◽

2018 ◽

Vol 20 (5) ◽

pp. S54 ◽

Cited By ~ 1

Author(s):

W. Tseng ◽

S. Hung ◽

C. Chien ◽

D. Tarng

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Renal Ischemia ◽

M2 Macrophage ◽

Renal Ischemia Reperfusion Injury ◽

Macrophage Subsets

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IL-4RA Signaling Regulates Liver Fibrosis Progression and Reversal Differently by Modulating Polarization of M2 Macrophage Subsets

Journal of Hepatology ◽

10.1016/s0168-8278(16)00927-2 ◽

2016 ◽

Vol 64 (2) ◽

pp. S526

Author(s):

S.Y. Weng ◽

S. Vijayan ◽

X. Wang ◽

Y. Tang ◽

K. Padberg ◽

...

Keyword(s):

Liver Fibrosis ◽

M2 Macrophage ◽

Fibrosis Progression ◽

Macrophage Subsets

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Regulation of liver fibrosis by tuning M2 macrophage signaling through IL-4Ralpha

Zeitschrift für Gastroenterologie ◽

10.1055/s-0033-1352811 ◽

2013 ◽

Vol 51 (08) ◽

Cited By ~ 1

Author(s):

SY Weng ◽

K Padberg ◽

YO Kim ◽

XY Wang ◽

M Mccaleb ◽

...

Keyword(s):

Liver Fibrosis ◽

M2 Macrophage

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PHENOTYPIC HETEROGENEITY OF CARDIAC MACROPHAGES DURING WOUND HEALING FOLLOWING MYOCARDIAL INFARCTION: PERSPECTIVES IN CLINICAL RESEARCH

Siberian Medical Journal ◽

10.29001/2073-8552-2018-33-2-70-76 ◽

2018 ◽

Vol 33 (2) ◽

pp. 70-76 ◽

Cited By ~ 1

Author(s):

A. E. Gombozhapova ◽

Yu. V. Rogovskaya ◽

M. S. Rebenkova ◽

J. G. Kzhyshkowska ◽

V. V. Ryabov

Keyword(s):

Myocardial Infarction ◽

Wound Healing ◽

Cardiac Remodeling ◽

Phenotypic Heterogeneity ◽

Macrophage Infiltration ◽

Myocardial Regeneration ◽

Control Group ◽

M2 Macrophage ◽

Inflammatory Phase ◽

Regenerative Phase

Purpose. Myocardial regeneration is one of the most ambitious goals in prevention of adverse cardiac remodeling. Macrophages play a key role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). We have accumulated data on macrophage properties ex vivo and in cell culture. However, there is no clear information about phenotypic heterogeneity of cardiac macrophages in patients with MI. The purpose of the project was to assess cardiac macrophage infiltration during wound healing following myocardial infarction in clinical settings taking into consideration experimental knowledge.Material and Methods. The study included 41 patients with fatal MI type 1. In addition to routine analysis, macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163, CD206, and stabilin-1 were considered as M2 macrophage biomarkers. Nine patients who died from noncardiovascular causes comprised the control group.Results. The intensity of cardiac macrophage infiltration was higher during the regenerative phase than during the inflammatory phase. Results of immunohistochemical analysis demonstrated the presence of phenotypic heterogeneity of cardiac macrophages in patients with MI. We noticed that numbers of CD68+, CD163+, CD206+, and stabilin-1+ macrophages depended on MI phase.Conclusion. Our study supports prospects for implementation of macrophage phenotyping in clinic practice. Improved understanding of phenotypic heterogeneity might become the basis of a method to predict adverse cardiac remodeling and the first step in developing myocardial regeneration target therapy.

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