Maternal monocytes in pregnancy and preeclampsia in humans and in rats

AbstractMonocytes are short-lived cells, arising from the bone marrow and maturing in the circulation. They play an important role in immune responses and are thought to be important for healthy pregnancy. In humans, 3 subpopulations of monocytes have been identified: classical, intermediate and non-classical monocytes. These subpopulations have different functions and phenotypical characteristics. Healthy pregnancy is characterized by a pro-inflammatory condition, with increased numbers of monocytes and monocyte activation as well as with increased numbers of intermediate monocytes and decreased numbers of classical monocytes. This may suggest monocyte maturation. Preeclampsia is an important pregnancy complication characterized by hypertension and proteinuria developing in the second half of pregnancy. The pathophysiology of preeclampsia is associated with further activation of the inflammatory response, further activation of monocytes and further monocyte maturation. In the present review we focus on the role of monocyte activation and maturation in healthy and preeclamptic pregnancy

Mitochondrial function in immune cells in health and disease

One of the main functions of mitochondria is production of ATP for cellular energy needs, however, it becomes more recognized that mitochondria are involved in differentiation and activation processes of immune cells. Upon activation, immune cells have a high need for energy. Immune cells have different strategies to generate this energy. In pro-inflammatory cells, such as activated monocytes and activated T and B cells, the energy is generated by increasing glycolysis, while in regulatory cells, such as regulatory T cells or M2 macrophages, energy is generated by increasing mitochondrial function and beta-oxidation. Except for being important for energy supply during activation, mitochondria also induce immune responses. During an infection, they release mitochondrial danger associated molecules (DAMPs) that resemble structures of bacterial derived pathogen associated molecular patterns (PAMPs). Such mitochondrial DAMPS are for instance mitochondrial DNA with hypomethylated CpG motifs or a specific lipid that is only present in prokaryotic bacteria and mitochondria, i.e. cardiolipin. Via release of such DAMPs, mitochondria guide the immune response towards an inflammatory response against pathogens. This is an important mechanism in early detection of an infection and in stimulating and sustaining immune responses to fight infections. However, mitochondrial DAMPs may also have a negative impact. If mitochondrial DAMPs are released by damaged cells, without the presence of an infection, such as after a trauma, mitochondrial DAMPs may induce an undesired inflammatory response, resulting in tissue damage and organ dysfunction. Thus, immune cells have developed mechanisms to prevent such undesired immune activation by mitochondrial components. In the present narrative review, we will describe the current view of mitochondria in regulation of immune responses. We will also discuss the current knowledge on disturbed mitochondrial function in immune cells in various immunological diseases

Estuarine fluid mud : its behavior and accumulation

A study of fluid mud in Virginia estuaries was conducted to determine how the mud accumulates in a dynamic tidal flow regime. The mud occurs as lenses and blanket deposits in zones of fast sedimentation, i.e. on channel floors and in the turbidity maximum zone. Viscosity measurements indicate resuspension potential of the mud is greater in the turbidity maximum than elsewhere

Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer's disease models.

Microglia activation has emerged as a potential key factor in the pathogenesis of Alzheimers disease. Metabolite levels assessed by magnetic resonance spectroscopy (MRS) are used as markers of neuroinflammation in neurodegenerative diseases, but how they relate to microglial activation in health and chronic disease is incompletely understood. Using MRS, we monitored the brain metabolic response to lipopolysaccharides (LPS)-induced microglia activation in vivo in a transgenic mouse model of Alzheimers disease (APP/PS1) and healthy controls (wild-type (WT) littermates) over 4 hours. We assessed reactive gliosis by immunohistochemistry and correlated metabolic and histological measures. In WT mice, LPS induced a microglial phenotype consistent with activation, associated with a sustained increase in macromolecule and lipid levels (ML9). This effect was not seen in APP/PS1 mice, where LPS did not lead to a microglial response measured by histology, but induced a late increase in the putative inflammation marker myoinositol (mI) and metabolic changes in total creatine and taurine previously reported to be associated with amyloid load. We argue that ML9 and mI distinguish the response of WT and APP/PS1 mice to immune mediators. Lipid and macromolecule levels may represent a biomarker of activation of healthy microglia, while mI may not be a glial marker

S100B brain expression and plasma concentrations in a preeclampsia rat model

Objective: To assess brain damage using the neuroinflammation marker S100B in a preeclampsia rat model.Methods: Non-pregnant and pregnant rats were infused with saline or low-dose-endotoxin on day 14 of pregnancy. S100B expression in the brain (immunohistochemistry) and S100B plasma concentrations (ELISA) were studied.Results: No differences in S100B expression in brain tissue were observed between the four groups. Pregnant endotoxin treated animals did not show increased levels of plasma S100B levels as compared with control pregnant rats, while significantly higher plasma S100B levels were found in non-pregnant endotoxin versus pregnant endotoxin infused rats.Conclusion: Pregnancy nor experimental preeclampsia, alter S100B in rat brain, or in plasma. Increased plasma S100B in non-pregnant endotoxin-treated rats may indicate brain injury in these rats, whereas pregnancy might be protective.</p

The effects of different dietary fiber pectin structures on the gastrointestinal immune barrier:impact via gut microbiota and direct effects on immune cells

Pectins are dietary fibers with different structural characteristics. Specific pectin structures can influence the gastrointestinal immune barrier by directly interacting with immune cells or by impacting the intestinal microbiota. The impact of pectin strongly depends on the specific structural characteristics of pectin; for example, the degree of methyl-esterification, acetylation and rhamnogalacturonan I or rhamnogalacturonan II neutral side chains. Here, we review the interactions of specific pectin structures with the gastrointestinal immune barrier. The effects of pectin include strengthening the mucus layer, enhancing epithelial integrity, and activating or inhibiting dendritic cell and macrophage responses. The direct interaction of pectins with the gastrointestinal immune barrier may be governed through pattern recognition receptors, such as Toll-like receptors 2 and 4 or Galectin-3. In addition, specific pectins can stimulate the diversity and abundance of beneficial microbial communities. Furthermore, the gastrointestinal immune barrier may be enhanced by short-chain fatty acids. Moreover, pectins can enhance the intestinal immune barrier by favoring the adhesion of commensal bacteria and inhibiting the adhesion of pathogens to epithelial cells. Current data illustrate that pectin may be a powerful dietary fiber to manage and prevent several inflammatory conditions, but additional human studies with pectin molecules with well-defined structures are urgently needed

Patented novelties in immunoisolation for the treatment of endocrine disorders

Immunoisolation is based on the principle that transplanted tissue is protected for the host immune system by an artificial membrane. During the past decades a number of different approaches of immunoisolation have been described. The approaches include (i) intravascular devices, which are anatomized to the vascular system, (ii) extravascular macrocapsules, which are mostly diffusion chambers transplanted at different sites, and (iii) extravascular microcapsules. Many reviews describing the advantages and pitfalls of the different approaches of immunoisolation have been described during recent years. Almost none of these reviews however describe the technical advances and (pre)clinical results described in the numerous patents on the subject. Therefore this review presents the recent novelties described in patents related to immunoisolation of tissue

Pancreatic Beta-Cell Purification by Altering FAD and NAD(P)H Metabolism

Isolation of primary beta cells from other cells within in the pancreatic islets is of importance for many fields of islet research. However, up to now, no satisfactory method has been developed that gained high numbers of viable beta cells, without considerable alpha-cell contamination. In this study, we investigated whether rat beta cells can be isolated from nonbeta endocrine cells by manipulating the flavin adenine dinucleotide (FAD) and nicotinamide-adenine dinucleotide phosphate (NAD(P)H) autofluorescence. Beta cells were isolated from dispersed islets by flow cytometry, based on their high FAD and NAD(P)H fluorescence. To improve beta cell yield and purity, the cellular FAD and NAD(P)H contents were altered by preincubation in culture media containing varying amounts of D-glucose and amino acids. Manipulation of the cellular FAD and NAD(P)H fluorescence improves beta cell yield and purity after sorting. This method is also a fast and reliable method to measure beta cell functional viability. A conceivable application is assessing beta cell viability before transplantation