scholarly journals Medawar’s PostEra: Galectins Emerged as Key Players During Fetal-Maternal Glycoimmune Adaptation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ellen Menkhorst ◽  
Nandor Gabor Than ◽  
Udo Jeschke ◽  
Gabriela Barrientos ◽  
Laszlo Szereday ◽  
...  
Keyword(s):  
Immune Cell ◽  
Successful Pregnancy ◽  
Fetal Health ◽  
The Past ◽  
Mammalian Embryogenesis ◽  
Carbohydrate Ligands ◽  
Membrane Bound

Lectin-glycan interactions, in particular those mediated by the galectin family, regulate many processes required for a successful pregnancy. Over the past decades, increasing evidence gathered from in vitro and in vivo experiments indicate that members of the galectin family specifically bind to both intracellular and membrane bound carbohydrate ligands regulating angiogenesis, immune-cell adaptations required to tolerate the fetal semi-allograft and mammalian embryogenesis. Therefore, galectins play important roles in fetal development and placentation contributing to maternal and fetal health. This review discusses the expression and role of galectins during the course of pregnancy, with an emphasis on maternal immune adaptions and galectin-glycan interactions uncovered in the recent years. In addition, we summarize the galectin fingerprints associated with pathological gestation with particular focus on preeclampsia.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Role of LecA and LecB Lectins in Pseudomonas aeruginosa-Induced Lung Injury and Effect of Carbohydrate Ligands

2009 ◽  
Vol 77 (5) ◽  
pp. 2065-2075 ◽  
Author(s):  
Chanez Chemani ◽  
Anne Imberty ◽  
Sophie de Bentzmann ◽  
Maud Pierre ◽  
Michaela Wimmerová ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Parental Strain ◽  
A549 Cells ◽  
Carbohydrate Ligands ◽  
Vitro Model

ABSTRACT Pseudomonas aeruginosa is a frequently encountered pathogen that is involved in acute and chronic lung infections. Lectin-mediated bacterium-cell recognition and adhesion are critical steps in initiating P. aeruginosa pathogenesis. This study was designed to evaluate the contributions of LecA and LecB to the pathogenesis of P. aeruginosa-mediated acute lung injury. Using an in vitro model with A549 cells and an experimental in vivo murine model of acute lung injury, we compared the parental strain to lecA and lecB mutants. The effects of both LecA- and Lec B-specific lectin-inhibiting carbohydrates (α-methyl-galactoside and α-methyl-fucoside, respectively) were evaluated. In vitro, the parental strain was associated with increased cytotoxicity and adhesion on A549 cells compared to the lecA and lecB mutants. In vivo, the P. aeruginosa-induced increase in alveolar barrier permeability was reduced with both mutants. The bacterial burden and dissemination were decreased for both mutants compared with the parental strain. Coadministration of specific lectin inhibitors markedly reduced lung injury and mortality. Our results demonstrate that there is a relationship between lectins and the pathogenicity of P. aeruginosa. Inhibition of the lectins by specific carbohydrates may provide new therapeutic perspectives.

Embryo biotechnology in the dog: a review

2010 ◽  
Vol 22 (7) ◽  
pp. 1049 ◽  
Author(s):  
Sylvie Chastant-Maillard ◽  
Martine Chebrout ◽  
Sandra Thoumire ◽  
Marie Saint-Dizier ◽  
Marc Chodkiewicz ◽  
...  
Keyword(s):  
Mammalian Species ◽  
Embryonic Stem ◽  
Reproductive Technologies ◽  
Reproductive Physiology ◽  
Biological Models ◽  
The Past ◽  
Fertilisation Rate

Canine embryos are a scarce biological material because of difficulties in collecting in vivo-produced embryos and the inability, to date, to produce canine embryos in vitro. The procedure for the transfer of in vivo-produced embryos has not been developed adequately, with only six attempts reported in the literature that have resulted in the birth of 45 puppies. In vitro, the fertilisation rate is particularly low (∼10%) and the incidence of polyspermy particularly high. So far, no puppy has been obtained from an in vitro-produced embryo. In contrast, cloning of somatic cells has been used successfully over the past 4 years, with the birth of 41 puppies reported in the literature, a yield that is comparable to that for other mammalian species. Over the same period, canine embryonic stem sells and transgenic cloned dogs have been obtained. Thus, the latest reproductive technologies are further advanced than in vitro embryo production. The lack of fundamental studies on the specific features of reproductive physiology and developmental biology in the canine is regrettable in view of the increasing role of dogs in our society and of the current demand for new biological models in biomedical technology.

scholarly journals Morphogenic Effects of Ezrin Require a Phosphorylation-Induced Transition from Oligomers to Monomers at the Plasma Membrane

2000 ◽  
Vol 150 (1) ◽  
pp. 193-204 ◽  
Author(s):  
Alexis Gautreau ◽  
Daniel Louvard ◽  
Monique Arpin
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Wild Type ◽  
Erm Proteins ◽  
Threonine Residue ◽  
Phosphorylation Event ◽  
Membrane Bound

ERM (ezrin, radixin, moesin) proteins act as linkers between the plasma membrane and the actin cytoskeleton. An interaction between their NH2- and COOH-terminal domains occurs intramolecularly in closed monomers and intermolecularly in head-to-tail oligomers. In vitro, phosphorylation of a conserved threonine residue (T567 in ezrin) in the COOH-terminal domain of ERM proteins disrupts this interaction. Here, we have analyzed the role of this phosphorylation event in vivo, by deriving stable clones producing wild-type, T567A, and T567D ezrin from LLC-PK1 epithelial cells. We found that T567A ezrin was poorly associated with the cytoskeleton, but was able to form oligomers. In contrast, T567D ezrin was associated with the cytoskeleton, but its distribution was shifted from oligomers to monomers at the membrane. Moreover, production of T567D ezrin induced the formation of lamellipodia, membrane ruffles, and tufts of microvilli. Both T567A and T567D ezrin affected the development of multicellular epithelial structures. Collectively, these results suggest that phosphorylation of ERM proteins on this conserved threonine regulates the transition from membrane-bound oligomers to active monomers, which induce and are part of actin-rich membrane projections.

Plastoquinone-9 biosynthesis in cyanobacteria differs from that in plants and involves a novel 4-hydroxybenzoate solanesyltransferase

2012 ◽  
Vol 442 (3) ◽  
pp. 621-629 ◽  
Author(s):  
Radin Sadre ◽  
Christian Pfaff ◽  
Stephan Buchkremer
Keyword(s):  
Biosynthetic Pathway ◽  
In Vitro Assays ◽  
Transport Chain ◽  
In Vivo Labelling ◽  
Membrane Bound ◽  
Transformation Processes ◽  
Synechocystis Sp

PQ-9 (plastoquinone-9) has a central role in energy transformation processes in cyanobacteria by mediating electron transfer in both the photosynthetic as well as the respiratory electron transport chain. The present study provides evidence that the PQ-9 biosynthetic pathway in cyanobacteria differs substantially from that in plants. We identified 4-hydroxybenzoate as being the aromatic precursor for PQ-9 in Synechocystis sp. PCC6803, and in the present paper we report on the role of the membrane-bound 4-hydroxybenzoate solanesyltransferase, Slr0926, in PQ-9 biosynthesis and on the properties of the enzyme. The catalytic activity of Slr0926 was demonstrated by in vivo labelling experiments in Synechocystis sp., complementation studies in an Escherichia coli mutant with a defect in ubiquinone biosynthesis, and in vitro assays using the recombinant as well as the native enzyme. Although Slr0926 was highly specific for the prenyl acceptor substrate 4-hydroxybenzoate, it displayed a broad specificity with regard to the prenyl donor substrate and used not only solanesyl diphosphate, but also a number of shorter-chain prenyl diphosphates. In combination with in silico data, our results indicate that Slr0926 evolved from bacterial 4-hydroxybenzoate prenyltransferases catalysing prenylation in the course of ubiquinone biosynthesis.

The role of pulmonary intravascular macrophages in porcine reproductive and respiratory syndrome virus infection

2000 ◽  
Vol 1 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Roongroje Thanawongnuwech ◽  
Patrick G. Halbur ◽  
Eileen L. Thacker
Keyword(s):  
Virus Titer ◽  
Respiratory Syndrome Virus ◽  
The Past ◽  
Current State ◽  
Viral Particles ◽  
Increased Susceptibility ◽  
Pulmonary Intravascular Macrophages

AbstractThe objective of this article is to summarize the current state of knowledge of the complex interaction of porcine reproductive and respiratory syndrome virus (PRRSV) and porcine pulmonary intravascular macrophages (PIMs). PIMs play an important role in pulmonary surveillance, and in the past few years we have investigated their role in PRRSV infection. PRRSV antigens and nucleic acids have been demonstrated in PIMs bothin vitroandin vivo. Examination of cultured PIMs infected with PRRSV revealed the accumulation of viral particles in the smooth-walled vesicles. PRRSV-infected PIMsin vitroyielded a virus titer similar to pulmonary alveolar macrophages. PRRSV infection induces either apoptosis or cell lysis of PIMs. Thein vitrobactericidal activity of PRRSV-infected PIMs is significantly decreased. Phagocytic activity of PIMs, as measured by pulmonary copper clearance, is significantly decreased in PRRSV-infected pigs. This evidence supports the hypothesis that PRRSV-induced damage to PIMs results in increased susceptibility to bacteremic diseases. Recent studies with PRRSV andStreptococcus suiscoinfection confirmed that PRRSV predisposes pigs toS. suisinfection and bacteremia. These results could explain the increase in bacterial respiratory diseases and septicemias observed in PRRSV-infected pigs.

scholarly journals Emerging era of microneedle array for pharmaceutical and biomedical applications: recent advances and toxicological perspectives

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shailesh Dugam ◽  
Rahul Tade ◽  
Rani Dhole ◽  
Sopan Nangare
Keyword(s):  
Biomedical Applications ◽  
Microneedle Array ◽  
Bioavailability Enhancement ◽  
Main Text ◽  
The Past ◽  
Recent Advancement ◽  
Insight Into

Abstract Background Microneedles (MNs) are the utmost unique, efficient, and minimally invasive inventions in the pharmaceutical field. Over the past decades, many scientists around the globe have reported MNs cautious because of their superb future in distinct areas. Concerning the wise use of MNs herein, we deal in depth with the present applications of MNs in drug delivery. Main text The present review comprises various fabrication materials and methods used for MN synthesis. The article also noted the distinctive advantages of these MNs, which holds huge potential for pharmaceutical and biomedical applications. The role of MNs in serving as a platform to treat various ailments has been explained accompanied by unusual approaches. The review also inculcates the pharmacokinetics of MNs, which includes permeation, absorption, and bioavailability enhancement. Besides this, the in vitro/in vivo toxicity, biosafety, and marketed product of MNs have been reviewed. We have also discussed the clinical trials and patents on the pharmaceutical applications of MNs in brief. Conclusion To sum up, this article gives insight into the MNs and provides a recent advancement in MNs, which pave the pathway for future pharmaceutical and biomedical applications. Graphical abstract Pharmaceutical and biomedical applications of MNs

The Role of Membrane Bound Complement in the Aggregation of Mammalian Platelets by Collagen

1975 ◽  
Author(s):  
B. V. Chater
Keyword(s):  
Electron Microscope ◽  
Light Microscopy ◽  
Complement System ◽  
Membrane Bound ◽  
The Complement System ◽  
Adhesion Of Platelets ◽  
Collagen Stimulation

It has been observed in dogs decomplemented with purified Cobra Venom Factor, that their platelets lose the ability to aggregate in response to collagen stimulation. Further investigation of the effect of CVF in vitro in man, dog and rabbit, and in vivo in dog, reveals that in each case CVF abolishes the collagen response of platelets, and that this effect is dose related. Resuspension of CVF inactivated platelets in plasma containing complement, results in a total return of sensitivity to collagen. Examination of CVF inactivated platelets with the electron microscope, fails to show any marked difference from control platelets. Serotonin granules are still present and the platelets retain a discoid appearance. Incubation of platelets with antibodies to Cl, C3 and C5, results in inhibition of the collagen response, this effect also being dose related. Light microscopy studies indicate that CVF does not affect the adhesion of platelets to collagen but appears to prevent subsequent aggregation. It is suggested that the complement system is involved in the induction of release by collagen, and that inhibition by CVF and anti-complement antibodies is the result of a blocking of the release reaction.

scholarly journals The role of GTP binding and hydrolysis at the atToc159 preprotein receptor during protein import into chloroplasts

2008 ◽  
Vol 183 (1) ◽  
pp. 87-99 ◽  
Author(s):  
Fei Wang ◽  
Birgit Agne ◽  
Felix Kessler ◽  
Danny J. Schnell
Keyword(s):  
Protein Import ◽  
Insertion Mutation ◽  
Approaches To Study ◽  
Direct Binding ◽  
Membrane Bound ◽  
Type Receptor ◽  
Isolated Chloroplasts

The majority of nucleus-encoded chloroplast proteins are targeted to the organelle by direct binding to two membrane-bound GTPase receptors, Toc34 and Toc159. The GTPase activities of the receptors are implicated in two key import activities, preprotein binding and driving membrane translocation, but their precise functions have not been defined. We use a combination of in vivo and in vitro approaches to study the role of the Toc159 receptor in the import reaction. We show that atToc159-A864R, a receptor with reduced GTPase activity, can fully complement a lethal insertion mutation in the ATTOC159 gene. Surprisingly, the atToc159-A864R receptor increases the rate of protein import relative to wild-type receptor in isolated chloroplasts by stabilizing the formation of a GTP-dependent preprotein binding intermediate. These data favor a model in which the atToc159 receptor acts as part of a GTP-regulated switch for preprotein recognition at the TOC translocon.

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