Monocytic Ontogeny of Regenerated Macrophages Characterizes the Mesotheliomagenic Responses to Carbon Nanotubes

Macrophages are not only derived from circulating blood monocytes or embryonic precursors but also expand by proliferation. The origin determines macrophage fate and functions in steady state and pathological conditions. Macrophages predominantly infiltrate fibre-induced mesothelioma tumors and contribute to cancer development. Here, we revealed their ontogeny by comparing the response to needle-like mesotheliomagenic carbon nanotubes (CNT-7) with tangled-like non-mesotheliomagenic CNT-T. In a rat peritoneal cavity model of mesothelioma, both CNT induced a rapid macrophage disappearance reaction (MDR) of MHCIIlow resident macrophages generating an empty niche available for macrophage repopulation. Macrophage depletion after mesotheliomagenic CNT-7 was followed by a substantial inflammatory reaction, and macrophage replenishment completed after 7 days. Thirty days after non-mesotheliomagenic CNT-T, macrophage repopulation was still incomplete and accompanied by a limited inflammatory reaction. Cell depletion experiments, flow cytometry and RNA-seq analysis demonstrated that, after mesotheliomagenic CNT-7 exposure, resident macrophages were mainly replaced by an influx of monocytes, which differentiated locally into MHCIIhigh inflammatory macrophages. In contrast, the low inflammatory response induced by CNT-T was associated by the accumulation of self-renewing MHCIIlow macrophages that initially derive from monocytes. In conclusion, the mesotheliomagenic response to CNT specifically relies on macrophage niche recolonization by monocyte-derived inflammatory macrophages. In contrast, the apparent homeostasis after non-mesotheliomagenic CNT treatment involves a macrophage regeneration by proliferation. Macrophage depletion and repopulation are thus decisive events characterizing the carcinogenic activity of particles and fibres.

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Transcriptome Profile Alterations with Carbon Nanotubes, Quantum Dots, and Silver Nanoparticles: A Review

Genes ◽

10.3390/genes12060794 ◽

2021 ◽

Vol 12 (6) ◽

pp. 794

Author(s):

Cullen Horstmann ◽

Victoria Davenport ◽

Min Zhang ◽

Alyse Peters ◽

Kyoungtae Kim

Keyword(s):

Carbon Nanotubes ◽

Quantum Dots ◽

High Throughput Sequencing ◽

The Body ◽

Rna Seq ◽

Mechanisms Of Toxicity ◽

Promising Tool ◽

Engineered Nanomaterial ◽

Next Generation Sequencing Ngs ◽

Transcriptomic Changes

Next-generation sequencing (NGS) technology has revolutionized sequence-based research. In recent years, high-throughput sequencing has become the method of choice in studying the toxicity of chemical agents through observing and measuring changes in transcript levels. Engineered nanomaterial (ENM)-toxicity has become a major field of research and has adopted microarray and newer RNA-Seq methods. Recently, nanotechnology has become a promising tool in the diagnosis and treatment of several diseases in humans. However, due to their high stability, they are likely capable of remaining in the body and environment for long periods of time. Their mechanisms of toxicity and long-lasting effects on our health is still poorly understood. This review explores the effects of three ENMs including carbon nanotubes (CNTs), quantum dots (QDs), and Ag nanoparticles (AgNPs) by cross examining publications on transcriptomic changes induced by these nanomaterials.

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The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction

Blood ◽

10.1182/blood.v46.1.51.51 ◽

1975 ◽

Vol 46 (1) ◽

pp. 51-64 ◽

Cited By ~ 35

Author(s):

AE Gassmann ◽

R van Furth

Keyword(s):

Inflammatory Reaction ◽

Peripheral Blood ◽

Low Dose ◽

Peritoneal Macrophages ◽

High Dose ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Azathioprine Treatment ◽

Monocytes And Macrophages ◽

Kinetics Of

Abstract The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24–48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.

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The Role of Beta 2 Integrins in Macrophage Migration During Resolution of Inflammation.

Blood ◽

10.1182/blood.v114.22.3600.3600 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3600-3600 ◽

Cited By ~ 1

Author(s):

Yevgeniya Kushchayeva ◽

Darya Mishchuk ◽

Tatiana Ugarova

Keyword(s):

Lymph Nodes ◽

Conflicts Of Interest ◽

Fold Increase ◽

Initial Population ◽

Blood Monocytes ◽

Resident Cell ◽

Low Levels ◽

Inflammatory Macrophages ◽

Β2 Integrins

Abstract Abstract 3600 Poster Board III-537 The mobilization of blood monocytes and their differentiation into macrophages during the immune-inflammatory response helps to prepare the tissue for resolution. During the resolution phase of inflammation macrophages do not die locally: some cells emigrate by draining lymphatics whereas some remain at the site of inflammation. The major myelo-monocytic integrin αMβ2 (Mac-1, CD11b/CD18), together with two related integrins αDβ2 (CD11d/CD18) and αXβ2 (CD11c/CD18), mediate critical adhesive reactions of monocyte/macrophages. However, the roles of these adhesion receptors in control of macrophage retention at sites of inflammation and their emigration to lymph nodes are unclear. Using a mouse model of sterile peritonitis induced by thioglycollate injection, we examined the dynamics of macrophage β2 integrins during the resolution phase of inflammation. Macrophages were defined by FACS analyses as a population of cells expressing αMβ2high, αDβ2+ and CD115+. The initial population of resident β2, positive for βDβ2 and negative for αXβ2. The thioglycollate-challenged mice showed a ∼4-fold increase in macrophages on day 3 followed by a progressive decrease to normal resident cell numbers by day 13. Expression of αMβ2 on macrophages on day 3 decreased by 2.5-fold as a result of dilution of the initial population of αMβ2high resident macrophages by infiltrating blood monocytes expressing αMβ2low. However, after day 3, the density of αMβ2 on macrophages gradually increased and by day 13 returned to the high levels characteristic of resident macrophages. By contrast, expression of αDβ2 and αXβ2 on inflammatory macrophages increased by 2-fold by day 6-9 compared to that on resident macrophages and then returned to the resident levels by day 3. Thus, although the number of macrophages decreased from day 3 to day 9 by several fold, the population of macrophages which remained in the peritoneum was enriched in cells expressing the high levels of αMβ2 and αDα2. Tracking migration of fluorescently labeled peritoneal cells demonstrated that a population of macrophages which leaves the inflamed peritoneum and enters lymph nodes consists of cells expressing low levels of αMβ2 and αDβ2. These data suggested that upregulation of β2 integrins, especially αMβ2, may be responsible for the retention of macrophages in the peritoneum. Indeed, the rate of macrophage emigration from the peritoneum in the αMβ2-deficient mice was significantly higher than that in wild-type mice. The results indicate that macrophage emigration from the inflamed site is controlled by the level of integrin αMβ2 and αDβ2 with low expressors being migratory and high expressors remaining in the peritoneum. The data also highlight the importance of integrins αDβ2 and αXβ2 as specific markers of inflammatory macrophages. Disclosures: No relevant conflicts of interest to declare.

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Balance of MafB and PU.1 specifies alternative macrophage or dendritic cell fate

Blood ◽

10.1182/blood-2004-04-1448 ◽

2005 ◽

Vol 105 (7) ◽

pp. 2707-2716 ◽

Cited By ~ 110

Author(s):

Youssef Bakri ◽

Sandrine Sarrazin ◽

Ulrich P. Mayer ◽

Silke Tillmanns ◽

Claus Nerlov ◽

...

Keyword(s):

Cell Fate ◽

Transcriptional Activity ◽

Blood Monocytes ◽

Myeloid Dendritic Cells ◽

Macrophage Differentiation ◽

Myeloid Progenitor ◽

Pathological Conditions ◽

Normal Human ◽

Expression And Activity ◽

Myeloid Progenitors

AbstractMacrophages and myeloid dendritic cells (DCs) represent alternative differentiation options of bone marrow progenitors and blood monocytes. This choice profoundly influences the immune response under normal and pathological conditions, but the underlying transcriptional events remain unresolved. Here, we show that experimental activation of the transcription factors PU.1 and MafB in transformed chicken myeloid progenitors triggered alternative DC or macrophage fate, respectively. PU.1 activation also was instructive for DC fate in the absence of cytokines in human HL-60 cell-derived myeloid progenitor and monocyte clones. Differentiation of normal human monocytes to DCs led to a rapid increase of PU.1 to high levels that preceded phenotypic changes, but no MafB expression, whereas monocyte-derived macrophages expressed MafB and only moderate levels of PU.1. DCs inducing levels of PU.1 inhibited MafB expression in monocytes, which appeared to be required for DC specification, since constitutive MafB expression inhibited DC differentiation. Consistent with this, PU.1 directly bound to MafB, inhibited its transcriptional activity in macrophages, and repressed its ability to induce macrophage differentiation in chicken myeloid progenitors. We propose that high PU.1 activity favors DCs at the expense of macrophage fate by inhibiting expression and activity of the macrophage factor MafB.

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The effect of azathioprine (Imuran) on the kinetics of monocytes and macrophages during the normal steady state and an acute inflammatory reaction

Blood ◽

10.1182/blood.v46.1.51.bloodjournal46151 ◽

1975 ◽

Vol 46 (1) ◽

pp. 51-64 ◽

Cited By ~ 2

Author(s):

AE Gassmann ◽

R van Furth

Keyword(s):

Inflammatory Reaction ◽

Peripheral Blood ◽

Low Dose ◽

Peritoneal Macrophages ◽

High Dose ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Azathioprine Treatment ◽

Monocytes And Macrophages ◽

Kinetics Of

The effect of azathioprine on the kinetics of peripheral blood monocytes and peritoneal macrophages was studied in normal mice and in mice in which an inflammatory reaction was provoked. Two dosage levels were used: a high dose of 200mg/kg which is the maximum tolerated daily dose in mice, and low dose of 3 mg/kg which is about equivalent to a nontoxic, immunosuppressive, anti-inflammatory dose in man. The number of peripheral blood monocytes decreases gradually during azathioprine treatment of normal mice, the extent and duration being dependent on the dose and duration of administered over a period of 9 days gives an almost complete reduction, and a low dose (3 mg/kg) given for the same period results in a reduction of about 50%. This effect seems to be reversible, because when treatment is stopped the number of monocytes starts to increase 24–48 hr later. The number of peritoneal macrophages is only affected when a high dose (200 mg/kg) is given over a long period; a low dose has virtually no effect. In mice in which an inflammatory reaction was prevoked in the peritoneal cavity, the normally occurring increase in the numbers of both peripheral blood monocytes and peritoneal macrophages was suppressed, the extent being dependent on the dose of azathioprine administered. Labeling studies with 3H-thymidine indicated that the reduction of peripheral blood monocytes and peritoneal macrophages in the inflammatory exudate is due to a diminished monocyte production.

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Phagocytosis of senescent neutrophils by human monocyte-derived macrophages and rabbit inflammatory macrophages.

Journal of Experimental Medicine ◽

10.1084/jem.156.2.430 ◽

1982 ◽

Vol 156 (2) ◽

pp. 430-442 ◽

Cited By ~ 195

Author(s):

S L Newman ◽

J E Henson ◽

P M Henson

Keyword(s):

Human Monocyte ◽

Mononuclear Phagocytes ◽

Polymorphonuclear Neutrophils ◽

Human Neutrophils ◽

Dependent Manner ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

In Vitro System ◽

Inflammatory Macrophages

An in vitro system to investigate the ability of macrophages to recognize and ingest senescent polymorphonuclear neutrophils has been used that uses chromium-labeled neutrophils and staining for myeloperoxidase (MPO). Human monocyte-derived macrophages obtained from in vitro cultures were able to recognize "aged" but not freshly isolated 51Cr-labeled human neutrophils and ingest them. Freshly isolated monocytes did not exhibit this property. Because the aged neutrophils were greater than 95% viable, death did not appear to be a prerequisite for recognition and ingestion. Serum was not required for the aging of the neutrophils, and when serum was used, different concentrations did not appear to effect the aging process; that is, neutrophils aged in different concentrations of serum were ingested equally. Phagocytosis of senescent neutrophils by macrophages occurred in a time-dependent manner and was also dependent on the number of neutrophils added. Monocyte-derived macrophages first exhibited the ability to phagocytose senescent neutrophils on the 3rd d of culture, with the percentage of active macrophages increasing through day 7. In experiments with rabbit mononuclear phagocytes, immune complex-induced inflammatory macrophages from the lung but not resident bronchoalveolar macrophages or peripheral blood monocytes were found to be capable of recognition and ingestion of senescent rabbit neutrophils. These data suggest that the monocyte maturation process, akin to that seen during inflammation, is necessary in vitro before macrophages recognize and remove senescent neutrophils.

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Human monocytes and macrophages regulate immune tolerance via integrin αvβ8–mediated TGFβ activation

Journal of Experimental Medicine ◽

10.1084/jem.20171491 ◽

2018 ◽

Vol 215 (11) ◽

pp. 2725-2736 ◽

Cited By ~ 33

Author(s):

Aoife Kelly ◽

Sezin Gunaltay ◽

Craig P. McEntee ◽

Elinor E. Shuttleworth ◽

Catherine Smedley ◽

...

Keyword(s):

Inflammatory Responses ◽

Integrin Expression ◽

Blood Monocytes ◽

Healthy Human ◽

Monocytes And Macrophages ◽

Health And Disease ◽

Inflammatory Bowel ◽

Intestinal Macrophage ◽

Inflammatory Macrophages ◽

Human Monocytes And Macrophages

Monocytes are crucial immune cells involved in regulation of inflammation either directly or via differentiation into macrophages in tissues. However, many aspects of how their function is controlled in health and disease are not understood. Here we show that human blood monocytes activate high levels of the cytokine TGFβ, a pathway that is not evident in mouse monocytes. Human CD14+, but not CD16+, monocytes activate TGFβ via expression of the integrin αvβ8 and matrix metalloproteinase 14, which dampens their production of TNFα in response to LPS. Additionally, when monocytes differentiate into macrophages, integrin expression and TGFβ-activating ability are maintained in anti-inflammatory macrophages but down-regulated in pro-inflammatory macrophages. In the healthy human intestine, integrin αvβ8 is highly expressed on mature tissue macrophages, with these cells and their integrin expression being significantly reduced in active inflammatory bowel disease. Thus, our data suggest that integrin αvβ8–mediated TGFβ activation plays a key role in regulation of monocyte inflammatory responses and intestinal macrophage homeostasis.

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Macrophages mediate lung inflammation in a mouse model of ischemic acute kidney injury

AJP Renal Physiology ◽

10.1152/ajprenal.00559.2010 ◽

2012 ◽

Vol 302 (4) ◽

pp. F421-F432 ◽

Cited By ~ 31

Author(s):

Christopher Altmann ◽

Ana Andres-Hernando ◽

Rachel H. McMahan ◽

Nilesh Ahuja ◽

Zhibin He ◽

...

Keyword(s):

Acute Kidney Injury ◽

Alveolar Macrophage ◽

Alveolar Macrophages ◽

Lung Inflammation ◽

Kidney Injury ◽

Capillary Leak ◽

Blood Monocytes ◽

Wild Type ◽

Macrophage Depletion ◽

Reduced Renal Function

Serum IL-6 is increased in acute kidney injury (AKI) and inhibition of IL-6 reduces AKI-mediated lung inflammation. We hypothesized that circulating monocytes produce IL-6 and that alveolar macrophages mediate lung inflammation after AKI via chemokine (CXCL1) production. To investigate systemic and alveolar macrophages in lung injury after AKI, sham operation or 22 min of renal pedicle clamping (AKI) was performed in three experimental settings: 1) systemic macrophage depletion via diphtheria toxin (DT) injection to CD11b-DTR transgenic mice, 2) DT injection to wild-type mice, and 3) alveolar macrophage depletion via intratracheal (IT) liposome-encapsulated clodronate (LEC) administration to wild-type mice. In mice with AKI and systemic macrophage depletion (CD11b-DTR transgenic administered DT) vs. vehicle-treated AKI, blood monocytes and lung interstitial macrophages were reduced, renal function was similar, serum IL-6 was increased, lung inflammation was improved, lung CXCL1 was reduced, and lung capillary leak was increased. In wild-type mice with AKI administered DT vs. vehicle, serum IL-6 was increased. In mice with AKI and alveolar macrophage depletion (IT-LEC) vs. AKI with normal alveolar macrophage content, blood monocytes and lung interstitial macrophages were similar, alveolar macrophages were reduced, renal function was similar, lung inflammation was improved, lung CXCL1 was reduced, and lung capillary leak was increased. In conclusion, administration of DT in AKI is proinflammatory, limiting the use of the DTR-transgenic model to study systemic effects of AKI. Mice with AKI and either systemic mononuclear phagocyte depletion or alveolar macrophage depletion had reduced lung inflammation and lung CXCL1, but increased lung capillary leak; thus, mononuclear phagocytes mediate lung inflammation, but they protect against lung capillary leak after ischemic AKI. Since macrophage activation and chemokine production are key events in the development of acute lung injury (ALI), these data provide further evidence that AKI may cause ALI.

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Poly(3-Hydroxybutyrate)-Multiwalled Carbon Nanotubes Electrospun Scaffolds Modified with Curcumin

Polymers ◽

10.3390/polym12112588 ◽

2020 ◽

Vol 12 (11) ◽

pp. 2588

Author(s):

Nader Tanideh ◽

Negar Azarpira ◽

Najmeh Sarafraz ◽

Shahrokh Zare ◽

Aida Rowshanghiyas ◽

...

Keyword(s):

Carbon Nanotubes ◽

Tissue Engineering ◽

Multiwalled Carbon Nanotubes ◽

Inflammatory Reaction ◽

3D Structure ◽

Hydrolytic Degradation ◽

Multiwalled Carbon ◽

Electrospun Scaffolds

Appropriate selection of suitable materials and methods is essential for scaffolds fabrication in tissue engineering. The major challenge is to mimic the structure and functions of the extracellular matrix (ECM) of the native tissues. In this study, an optimized 3D structure containing poly(3-hydroxybutyrate) (P3HB), multiwalled carbon nanotubes (MCNTs) and curcumin (CUR) was created by electrospinning a novel biomimetic scaffold. CUR, a natural anti-inflammatory compound, has been selected as a bioactive component to increase the biocompatibility and reduce the potential inflammatory reaction of electrospun scaffolds. The presence of CUR in electrospun scaffolds was confirmed by 1H NMR and Fourier-transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) revealed highly interconnected porosity of the obtained 3D structures. Addition of up to 20 wt% CUR has enhanced mechanical properties of the scaffolds. CUR has also promoted in vitro bioactivity and hydrolytic degradation of the electrospun nanofibers. The developed P3HB-MCNT composite scaffolds containing 20 wt% of CUR revealed excellent in vitro cytocompatibility using mesenchymal stem cells and in vivo biocompatibility in rat animal model study. Importantly, the reduced inflammatory reaction in the rat model after 8 weeks of implantation has also been observed for scaffolds modified with CUR. Overall, newly developed P3HB-MCNTs-CUR electrospun scaffolds have demonstrated their high potential for tissue engineering applications.

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Fractalkine Preferentially Mediates Arrest and Migration of CD16+ Monocytes

Journal of Experimental Medicine ◽

10.1084/jem.20022156 ◽

2003 ◽

Vol 197 (12) ◽

pp. 1701-1707 ◽

Cited By ~ 368

Author(s):

Petronela Ancuta ◽

Ravi Rao ◽

Ashlee Moses ◽

Andrew Mehle ◽

Sunil K. Shaw ◽

...

Keyword(s):

Chemokine Receptors ◽

Molecular Mechanisms ◽

Tissue Injury ◽

Monocyte Subset ◽

Blood Monocytes ◽

Monocyte Chemoattractant Protein 1 ◽

Pathological Conditions ◽

Normal Individuals ◽

And Migration

CD16+ monocytes represent 5–10% of peripheral blood monocytes in normal individuals and are dramatically expanded in several pathological conditions including sepsis, human immunodeficiency virus 1 infection, and cancer. CD16+ monocytes produce high levels of proinflammatory cytokines and may represent dendritic cell precursors in vivo. The mechanisms that mediate the recruitment of CD16+ monocytes into tissues remain unknown. Here we investigate molecular mechanisms of CD16+ monocyte trafficking and show that migration of CD16+ and CD16− monocytes is mediated by distinct combinations of adhesion molecules and chemokine receptors. In contrast to CD16− monocytes, CD16+ monocytes expressed high CX3CR1 and CXCR4 but low CCR2 and CD62L levels and underwent efficient transendo-thelial migration in response to fractalkine (FKN; FKN/CX3CL1) and stromal-derived factor 1α (CXCL12) but not monocyte chemoattractant protein 1 (CCL2). CD16+ monocytes arrested on cell surface–expressed FKN under flow with higher frequency compared with CD16− monocytes. These results demonstrate that FKN preferentially mediates arrest and migration of CD16+ monocytes and suggest that recruitment of this proinflammatory monocyte subset to vessel walls via the CX3CR1-FKN pathway may contribute to vascular and tissue injury during pathological conditions.

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