scholarly journals Diversity, Mechanisms, and Significance of Macrophage Plasticity

2020 ◽  
Vol 15 (1) ◽  
pp. 123-147 ◽  
Author(s):  
Massimo Locati ◽  
Graziella Curtale ◽  
Alberto Mantovani
Keyword(s):  
Single Cell Analysis ◽  
Wide Spectrum ◽  
Mononuclear Phagocytes ◽  
Adaptive Responses ◽  
Metabolic Derangement ◽  
Microbial Invasion ◽  
Microrna Networks ◽  
Health And Disease ◽  
Macrophage Plasticity ◽  
Body Compartments

Macrophages are a diverse set of cells present in all body compartments. This diversity is imprinted by their ontogenetic origin (embryonal versus adult bone marrow–derived cells); the organ context; by their activation or deactivation by various signals in the contexts of microbial invasion, tissue damage, and metabolic derangement; and by polarization of adaptive T cell responses. Classic adaptive responses of macrophages include tolerance, priming, and a wide spectrum of activation states, including M1, M2, or M2-like. Moreover, macrophages can retain long-term imprinting of microbial encounters (trained innate immunity). Single-cell analysis of mononuclear phagocytes in health and disease has added a new dimension to our understanding of the diversity of macrophage differentiation and activation. Epigenetic landscapes, transcription factors, and microRNA networks underlie the adaptability of macrophages to different environmental cues. Macrophage plasticity, an essential component of chronic inflammation, and its involvement in diverse human diseases, most notably cancer, is discussed here as a paradigm.

EFFECTIVENESS AND TOLERABILITY OF CV-3988, A SELECTIVE PAF ANTAGONIST, AFTER INTRAVENOUS ADMINISTRATION TO MAN

1987 ◽  
Author(s):  
J Arnout ◽  
A Van Hecken ◽  
I Delepeleire ◽  
Y Miyamoto ◽  
I Holmes ◽  
...  
Keyword(s):  
Light Transmission ◽  
Platelet Rich Plasma ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Platelet Activating Factor ◽  
Controlled Study ◽  
Dependent Manner ◽  
Double Blind ◽  
Health And Disease

Platelet activating factor (PAF) is a naturally occurring phospholipid with a wide spectrum of biological activities. Although PAF has been ascribed a potential role in various conditions including inflammation, asthma, glomerulonephritis and thrombosis, its precise function in physiologic/pathophysiologic processes remains unclear. The introduction of selective PAF receptor antagonists could represent a useful tool to extend our knowledge of the role of this mediator in health and disease.We have investigated the efficacy and tolerability of (RS)-2-methoxy-3-(octadecylcarbomoyloxy)propy1 2-(3-thiazolio)-ethyIphosphate (CV-3988, Takeda Chem. Ind), a selective PAF antagonist with structural analogies with PAF, after intravenous infusion in man in a double-blind, placebo-controlled study. The compound, in doses from 750 to 2,000 pg/kg, significantly reduced platelet sensitivity to PAF. The threshold aggregating concentration (TAC) of PAF was defined as the minimal concentration causing an irreversible aggregation with a maximal amplitude of at least 50% of the difference in light transmission between platelet rich plasma and platelet poor plasma. It increased in a dose-dependent manner reaching 3.6 times the basal TAC (p<0.0005) at the end and 2.60 times the basal TAC (p<0.0005) 4 hours after infusion of the highest dose. The TAC of PAF returned to the basal value within 24 hours after the end of the infusion.CV-3988 did not cause major side effects nor changes in blood pressure, pulse or respiratory rate. However, small but clinically insignificant changes in plasma haemoglobin and serum haptoglobin were seen at the end and four hours after the end of the infusion, indicating a slight haemolysis probably by high local concentrations at the infusion site.Our results indicate that, when adequate infusion volumes and infusion rates are used, CV-3988 can be safely administered to man and should be useful in elucidating the role of PAF in health and disease.

scholarly journals Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease

2019 ◽  
Vol 216 (3) ◽  
pp. 482-500 ◽  
Author(s):  
Kyle Tretina ◽  
Eui-Soon Park ◽  
Agnieszka Maminska ◽  
John D. MacMicking
Keyword(s):  
Innate Immunity ◽  
Bacterial Infection ◽  
Host Defense ◽  
Tissue Damage ◽  
Binding Proteins ◽  
Wide Spectrum ◽  
Cell Types ◽  
Microbial Pathogens ◽  
Health And Disease ◽  
Basic Biology

Guanylate-binding proteins (GBPs) have recently emerged as central orchestrators of immunity to infection, inflammation, and neoplastic diseases. Within numerous host cell types, these IFN-induced GTPases assemble into large nanomachines that execute distinct host defense activities against a wide variety of microbial pathogens. In addition, GBPs customize inflammasome responses to bacterial infection and sepsis, where they act as critical rheostats to amplify innate immunity and regulate tissue damage. Similar functions are becoming evident for metabolic inflammatory syndromes and cancer, further underscoring the importance of GBPs within infectious as well as altered homeostatic settings. A better understanding of the basic biology of these IFN-induced GTPases could thus benefit clinical approaches to a wide spectrum of important human diseases.

scholarly journals Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Immunity ◽  
2019 ◽  
Vol 51 (3) ◽  
pp. 573-589.e8 ◽  
Author(s):  
Charles-Antoine Dutertre ◽  
Etienne Becht ◽  
Sergio Erdal Irac ◽  
Ahad Khalilnezhad ◽  
Vipin Narang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Single Cell ◽  
Single Cell Analysis ◽  
Mononuclear Phagocytes ◽  
Cell Analysis ◽  
Inflammatory Dendritic Cells

scholarly journals The Roles of PPARs in the Fetal Origins of Metabolic Health and Disease

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
William D. Rees ◽  
Christopher J. McNeil ◽  
Christopher A. Maloney
Keyword(s):  
Epigenetic Modification ◽  
Fetal Liver ◽  
Maternal Diet ◽  
Subsequent Development ◽  
Adaptive Responses ◽  
Fetal Origins ◽  
Methylation Of Dna ◽  
Health And Disease ◽  
Cell Growth And Differentiation

Beyond the short-term effects on fertility, there is increasing evidence that obesity or the consumption of an inappropriate diet by the mother during pregnancy adversely affects the long-term health of her offspring. PPAR and RXR isotypes are widely expressed in reproductive tissues and in the developing fetus. Through their interactions with fatty acids, they may mediate adaptive responses to the changes in the maternal diet. In the maturing follicle, PPAR-γhas an important role in the granulosa cells that surround the maturing oocyte. After fertilisation, PPAR-γand PPAR-β/δare essential regulators of placentation and the subsequent development of key metabolic tissues such as skeletal muscle and adipose cells. Activation of PPAR-γand PPAR-β/δduring fetal development has the potential to modify the growth and development of these tissues. PPAR-αis expressed at low levels in the fetal liver, however, this expression may be important, as changes in the methylation of DNA in its promoter region are reported to take place during this period of development. This epigenetic modification then programmes subsequent expression. These findings suggest that two separate PPAR-dependent mechanisms may be involved in the fetal adaptations to the maternal diet, one, mediated by PPAR-γand PPAR-β/δ, regulating cell growth and differentiation; and another adapting long-term lipid metabolism via epigenetic changes in PPAR-αto optimise postnatal survival.

Intestinal Mononuclear Phagocytes in Health and Disease

2017 ◽  
pp. 687-700
Author(s):  
Theodore J. Sanders ◽  
Ulf Yrlid ◽  
Kevin J. Maloy
Keyword(s):  
Mononuclear Phagocytes ◽  
Health And Disease

Abstract 19088: Independent Association of Lipoprotein Sub-fractions by Ion Mobility Analysis with Anthropometric and Ectopic Visceral fat on Cardiac CT Examinations in a High risk Population: The Baptist Employee Healthy Heart Study (BEHHS)

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ebenezer T Oni ◽  
Ehimen C Aneni ◽  
Emir Veledar ◽  
Lara Roberson ◽  
Gagandeep Nagi ◽  
...  
Keyword(s):  
Ion Mobility ◽  
Visceral Fat ◽  
Robust Regression ◽  
Wide Spectrum ◽  
Multivariate Regression Analysis ◽  
Type Ii Diabetes Mellitus ◽  
High Risk Population ◽  
Cvd Risk ◽  
Metabolic Derangement ◽  
Heart Study

Introduction: Visceral adiposity is associated with increased CVD risk. Ectopic fat deposition is linked with lipotoxicity, metabolic derangement, insulin resistance, and atherosclerosis. The lipoprotein(LP) subclasses are established risk markers for CVD mortality. We evaluated for the association of ectopic visceral fat measures [pericardial (PCF), Epicardial (EPC)], traditional adiposity measures [waist: hip ratio (WHR), Body Mass index (BMI), waist circumference (WC)] and the LP subclasses. Methods: The Baptist Employee Healthy Heart Study (BEHHS) an ongoing study examines the effect of web based interventions on reducing CVD risk in subjects with metabolic syndrome and type II diabetes mellitus. We measured PCF and EPC adipose tissue volumes from the 16-slice multi-detector computed tomography (MDCT) (GE AWW 3D Workstation). Cardio IQ™ Ion Mobility LP fractionation was utilized for advanced lipid subclass measurement resulting in direct quantification of particles in each LP sub-class fraction. Results: The population had 182 participants, 74% women, 49% Hispanic, mean age of 52 ± 9 years. The median PCF volume was 130 (97-166) cc, EPC volume 112(78-265) cc, mean WC 105±15 cm, BMI 34±6 kg/m2 ,WHR was 0.94 (SD 0.09). There was no correlation between BMI, and WC with any of the LP. WHR was significantly correlated with LDL particle size LDL large (A), , IDL small, and HDL large, see table 1. These associations were not significant in multivariate regression analysis. On the other hand PCF and ECP were significantly correlated with a wide spectrum of the LPs. After an adjusted robust regression, they remained significantly associated with IDL(large), LDL(total), VLDL(small), VLDL(medium) and VLDL(large). Conclusion: This demonstrates association between the ectopic adiposity and LP subclasses compared to traditional obesity measures. Further follow-up is needed to assess the interplay of lifestyle intervention in improving cardiometabolic profile

scholarly journals Developmental Programming of the Metabolic Syndrome: Can We Reprogram with Resveratrol?

2018 ◽  
Vol 19 (9) ◽  
pp. 2584 ◽  
Author(s):  
You-Lin Tain ◽  
Chien-Ning Hsu
Keyword(s):  
Metabolic Syndrome ◽  
Early Life ◽  
Wide Spectrum ◽  
Molecular Targets ◽  
Developmental Programming ◽  
Developmental Origins ◽  
Polyphenolic Compound ◽  
Beneficial Effects ◽  
The Metabolic Syndrome ◽  
Health And Disease

Metabolic syndrome (MetS) is a mounting epidemic worldwide. MetS can start in early life, in a microenvironment that is now known as the developmental origins of health and disease (DOHaD). The concept of DOHaD also offers opportunities for reprogramming strategies that aim to reverse programming processes in early life. Resveratrol, a polyphenolic compound has a wide spectrum of beneficial effects on human health. In this review, we first summarize the epidemiological and experimental evidence supporting the developmental programming of MetS. This review also presents an overview of the evidence linking different molecular targets of resveratrol to developmental programming of MetS-related disorders. This will be followed by studies documenting resveratrol as a reprogramming agent to protect against MetS-related disorders. Further clinical studies are required in order to bridge the gap between animal models and clinical trials in order to establish the effective dose and therapeutic duration for resveratrol as a reprogramming therapy on MetS disorders from developmental origins.

Macrophage plasticity, polarization, and function in health and disease

2018 ◽  
Vol 233 (9) ◽  
pp. 6425-6440 ◽  
Author(s):  
Abbas Shapouri-Moghaddam ◽  
Saeed Mohammadian ◽  
Hossein Vazini ◽  
Mahdi Taghadosi ◽  
Seyed-Alireza Esmaeili ◽  
...  
Keyword(s):  
Health And Disease ◽  
Macrophage Plasticity ◽  
And Function

scholarly journals Complex Microbiota in Laboratory Rodents: Management Considerations

ILAR Journal ◽  
2019 ◽  
Vol 60 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Craig L Franklin ◽  
Aaron C Ericsson
Keyword(s):  
Microbial Communities ◽  
Animal Health ◽  
Turn Of The Century ◽  
The Body ◽  
Research Subjects ◽  
Next Generation Sequencing Technology ◽  
Laboratory Rodents ◽  
Health And Disease ◽  
Body Compartments

Abstract Our bodies and those of our animal research subjects are colonized by bacterial communities that occupy virtually every organ system, including many previously considered sterile. These bacteria reside as complex communities that are collectively referred to as microbiota. Prior to the turn of the century, characterization of these communities was limited by a reliance on culture of organisms on a battery of selective media. It was recognized that the vast majority of microbes, especially those occupying unique niches of the body such as the anaerobic environment of the intestinal tract, were uncultivatable. However, with the onset and advancement of next-generation sequencing technology, we are now capable of characterizing these complex communities without the need to cultivate, and this has resulted in an explosion of information and new challenges in interpreting data generated about, and in the context of, these complex communities. We have long known that these microbial communities often exist in an intricate balance that, if disrupted (ie, dysbiosis), can lead to disease or increased susceptibility to disease. Because of many functional redundancies, the makeup of these colonies can vary dramatically within healthy individuals [1]. However, there is growing evidence that subtle differences can alter the phenotype of various animal models, which may translate to the varying susceptibility to disease seen in the human population. In this manuscript, we discuss how to include complex microbiota as a consideration in experimental design and model reproducibility and how to exploit the extensive variation that exists in contemporary rodent research colonies. Our focus will be the intestinal or gut microbiota (GM), but it should be recognized that microbial communities exist in many other body compartments and these too likely influence health and disease [2, 3]. Much like host genetics, can we one day harness the vast genetic capacity of the microbes we live with in ways that will benefit human and animal health?

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