scholarly journals A Helminth-Derived Chitinase Structurally Similar to Mammalian Chitinase Displays Immunomodulatory Properties in Inflammatory Lung Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Friederike Ebner ◽  
Katja Lindner ◽  
Katharina Janek ◽  
Agathe Niewienda ◽  
Piotr H. Malecki ◽  
...  
Keyword(s):  
Cell Activation ◽  
Disease Model ◽  
Three Dimensional ◽  
Clinical Signs ◽  
Gastrointestinal Nematode ◽  
Chitinase Activity ◽  
Airway Hyperreactivity ◽  
Allergic Airway Disease ◽  
Dimensional Structure ◽  
Dendritic Cell Activation

Immunomodulation of airway hyperreactivity by excretory-secretory (ES) products of the first larval stage (L1) of the gastrointestinal nematode Trichuris suis is reported by us and others. Here, we aimed to identify the proteins accounting for the modulatory effects of the T. suis L1 ES proteins and studied six selected T. suis L1 proteins for their immunomodulatory efficacy in a murine OVA-induced allergic airway disease model. In particular, an enzymatically active T. suis chitinase mediated amelioration of clinical signs of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung, the associated chemokines, and increased numbers of RELMα+ interstitial lung macrophages. While there is no indication of T. suis chitinase directly interfering with dendritic cell activation or antigen presentation to CD4 T cells, treatment of allergic mice with the worm chitinase influenced the hosts’ own chitinase activity in the inflamed lung. The three-dimensional structure of the T. suis chitinase as determined by high-resolution X-ray crystallography revealed high similarities to mouse acidic mammalian chitinase (AMCase) but a unique ability of T. suis chitinase to form dimers. Our data indicate that the structural similarities between the parasite and host chitinase contribute to the disease-ameliorating effect of the helminth-derived chitinase on allergic lung inflammation.

scholarly journals A helminth chitinase structurally similar to mammalian chitinase displays immunomodulatory properties

2019 ◽  
Author(s):  
Friederike Ebner ◽  
Katja Balster ◽  
Katharina Janek ◽  
Agathe Niewienda ◽  
Piotr H. Malecki ◽  
...  
Keyword(s):  
Inflammatory Marker ◽  
Disease Model ◽  
Three Dimensional ◽  
Gastrointestinal Nematode ◽  
Airway Hyperreactivity ◽  
Allergic Airway Disease ◽  
Biologically Active ◽  
Dimensional Structure ◽  
Trichuris Suis ◽  
Immunomodulatory Properties

AbstractPreviously, we reported significant immunomodulatory effects of the entire excretory-secretory (ES) proteins of the first larval stage (L1) of the gastrointestinal nematodeTrichuris suisin a rodent model of allergic hyperreactivity. In the present study, we aimed to identify the proteins accounting for the modulatory effects of theT. suisL1 ES proteins and thus studied selected components for their immunomodulatory efficacy in an OVA-induced allergic airway disease model. In particular, an enzymatically activeT. suischitinase mediated amelioration of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung. The three-dimensional structure of theT. suischitinase as determined by high-resolution X-ray crystallography revealed significant similarities to mouse acidic mammalian chitinase (AMCase). In addition, the unique ability ofT. suischitinase to form dimers, as well as acidic surface patches within the dimerization region may contribute to the formation of cross-reactive antibodies to the mouse homologs. This hypothesis is supported by the observation thatT. suischitinase treatment induced cross-reactive antibodies to mouse AMCase and chitinase-like protein BRP-39 in the AHR model. In conclusion, a biologically activeT. suischitinase exhibits immunomodulatory properties despite its structural similarity to the mammalian counterpart.Author summaryExperimental immunotherapy via reintroduction of intestinal worms to treat and prevent autoimmune, chronic inflammatory or allergic diseases is being discussed but the underlying mechanisms are still not fully understood. Here, we investigated the immunomodulatory potential of specific proteins of the whipwormTrichuris suisthat are secreted very early during larval development. Using a murine model of allergic lung disease, we show that in particular oneT. suisprotein, functionally characterized as an active chitinase, is reducing the lung inflammation. TheT. suischitinases three-dimensional protein structure revealed remarkable similarities to the hosts’ chitinase, an enzyme known to play a pivotal role in lung allergy. We also show that treatment with the helminth chitinase induced cross-reactive antibody responses against murine chitinase and chitinase-like proteins, both being inflammatory marker and regulators of type 2 immunity. Thus, our study provides a novel mechanism of immunomodulation by helminth components and may contribute to a better understanding of clinical responses of patients receiving helminthic therapy.

scholarly journals Three-Dimensional In Vitro Lymphangiogenesis Model in Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Youngkyu Cho ◽  
Kyuhwan Na ◽  
Yesl Jun ◽  
Jihee Won ◽  
Ji Hun Yang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Metastasis ◽  
Lymphatic Vessel ◽  
Disease Model ◽  
Three Dimensional ◽  
Lymphatic Vessels ◽  
Dimensional Structure ◽  
Biomechanical Stress

Lymphangiogenesis is a stage of new lymphatic vessel formation in development and pathology, such as inflammation and tumor metastasis. Physiologically relevant models of lymphatic vessels have been in demand because studies on lymphatic vessels are required for understanding the mechanism of tumor metastasis. In this study, a new three-dimensional lymphangiogenesis model in a tumor microenvironment is proposed, using a newly designed macrofluidic platform. It is verified that controllable biochemical and biomechanical cues, which contribute to lymphangiogenesis, can be applied in this platform. In particular, this model demonstrates that a reconstituted lymphatic vessel has an in vivo–like lymphatic vessel in both physical and biochemical aspects. Since biomechanical stress with a biochemical factor influences robust directional lymphatic sprouting, whether our model closely approximates in vivo, the initial lymphatics in terms of the morphological and genetic signatures is investigated. Furthermore, attempting an incorporation with a tumor spheroid, this study successfully develops a complex tumor microenvironment model for use in lymphangiogenesis and reveals the microenvironment factors that contribute to tumor metastasis. As a first attempt at a coculture model, this reconstituted model is a novel system with a fully three-dimensional structure and can be a powerful tool for pathological drug screening or disease model.

scholarly journals Potent and Selective Antitumor Activity of a T-Cell Engaging Bispecific Antibody Targeting a Membrane-Proximal Epitope of ROR1

2017 ◽  
Author(s):  
Junpeng Qi ◽  
Xiuling Li ◽  
Haiyong Peng ◽  
HaJeung Park ◽  
Christoph Rader
Keyword(s):  
T Cell ◽  
Antitumor Activity ◽  
Tumor Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Three Dimensional ◽  
Bispecific Antibodies ◽  
Dimensional Structure

AbstractT-cell engaging bispecific antibodies present a promising strategy for cancer immunotherapy and numerous bispecific formats have been developed for retargeting cytolytic T cells toward tumor cells. To explore the therapeutic utility of T-cell engaging bispecific antibodies targeting the receptor tyrosine kinase ROR1, which is expressed by tumor cells of various hematologic and solid malignancies, we used a bispecific ROR1 × CD3 scFv-Fc format based on a heterodimeric and aglycosylated Fc domain designed for extended circulatory half-life and diminished systemic T-cell activation. A diverse panel of ROR1-targeting scFv derived from immune and naïve rabbit antibody repertoires was compared in this bispecific format for target-dependent T-cell recruitment and activation. A ROR1-targeting scFv with a membrane-proximal epitope, R11, revealed potent and selective antitumor activity in vitro and in vivo and emerged as a prime candidate for further preclinical and clinical studies. To elucidate the precise location and engagement of this membrane-proximal epitope, which is conserved between human and mouse ROR1, the three-dimensional structure of scFv R11 in complex with the kringle domain of ROR1 was determined by X-ray crystallography at 1.6-Å resolution.

Conformation of Ribosomes from Escherichia Coli

1974 ◽  
Vol 32 ◽  
pp. 210-211
Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins
Keyword(s):  
Binding Sites ◽  
Ribosomal Proteins ◽  
Fluorescent Dyes ◽  
Protein Biosynthesis ◽  
Three Dimensional ◽  
Spatial Arrangement ◽  
Dimensional Structure ◽  
Complete Understanding ◽  
And Function

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.

Three-Dimensional Reconstruction Using Stereo Pairs from Serial Thick Sections

1977 ◽  
Vol 35 ◽  
pp. 562-563
Author(s):  
Robert Glaeser ◽  
Thomas Bauer ◽  
David Grano
Keyword(s):  
Three Dimensional ◽  
Dimensional Structure ◽  
Serial Sections ◽  
Thin Sections ◽  
3 Dimensional ◽  
Transmission Electron ◽  
Freeze Dried ◽  
Dimensional Reconstruction ◽  
Stereo Imagery ◽  
Whole Mounts

In transmission electron microscopy, the 3-dimensional structure of an object is usually obtained in one of two ways. For objects which can be included in one specimen, as for example with elements included in freeze- dried whole mounts and examined with a high voltage microscope, stereo pairs can be obtained which exhibit the 3-D structure of the element. For objects which can not be included in one specimen, the 3-D shape is obtained by reconstruction from serial sections. However, without stereo imagery, only detail which remains constant within the thickness of the section can be used in the reconstruction; consequently, the choice is between a low resolution reconstruction using a few thick sections and a better resolution reconstruction using many thin sections, generally a tedious chore. This paper describes an approach to 3-D reconstruction which uses stereo images of serial thick sections to reconstruct an object including detail which changes within the depth of an individual thick section.

Electron Microscopy of Cytoplasmic Contractile Proteins

1978 ◽  
Vol 36 (3) ◽  
pp. 606-614 ◽  
Author(s):  
T.D. Pollard ◽  
P. Maupin
Keyword(s):  
Electron Microscopy ◽  
Actin Filaments ◽  
Three Dimensional ◽  
Uranyl Acetate ◽  
Contractile Proteins ◽  
Dimensional Structure ◽  
X Ray Diffraction ◽  
Cytoplasmic Matrix ◽  
Computer Image Processing ◽  
Nonmuscle Cells

In this paper we review some of the contributions that electron microscopy has made to the analysis of actin and myosin from nonmuscle cells. We place particular emphasis upon the limitations of the ultrastructural techniques used to study these cytoplasmic contractile proteins, because it is not widely recognized how difficult it is to preserve these elements of the cytoplasmic matrix for electron microscopy. The structure of actin filaments is well preserved for electron microscope observation by negative staining with uranyl acetate (Figure 1). In fact, to a resolution of about 3nm the three-dimensional structure of actin filaments determined by computer image processing of electron micrographs of negatively stained specimens (Moore et al., 1970) is indistinguishable from the structure revealed by X-ray diffraction of living muscle.

A New 1000kv Electron Microscope

1969 ◽  
Vol 27 ◽  
pp. 100-101
Author(s):  
J.L. Williams ◽  
K. Heathcote ◽  
E.J. Greer
Keyword(s):  
Electron Microscope ◽  
Direct Observation ◽  
High Voltage ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Specimen Thickness ◽  
Voltage Electron ◽  
High Voltage Electron Microscope ◽  
Dynamic Experiments ◽  
Conventional Instrument

High Voltage Electron Microscope already offers exciting experimental possibilities to Biologists and Materials Scientists because the increased specimen thickness allows direct observation of three dimensional structure and dynamic experiments on effectively bulk specimens. This microscope is designed to give maximum accessibility and space in the specimen region for the special stages which are required. At the same time it provides an ease of operation similar to a conventional instrument.

High-voltage electron microscopy of maxillary gland of spirochete-infected brine shrimp: lesion of efferent tubule

1988 ◽  
Vol 46 ◽  
pp. 362-363
Author(s):  
G. E. Tyson ◽  
M. J. Song
Keyword(s):  
Electron Microscopy ◽  
High Voltage ◽  
Brine Shrimp ◽  
Natural Populations ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
High Voltage Electron Microscopy ◽  
Voltage Electron ◽  
High Voltage Electron ◽  
Infected Adult

Natural populations of the brine shrimp, Artemia, may possess spirochete- infected animals in low numbers. The ultrastructure of Artemia's spirochete has been described by conventional transmission electron microscopy. In infected shrimp, spirochetal cells were abundant in the blood and also occurred intra- and extracellularly in the three organs examined, i.e. the maxillary gland (segmental excretory organ), the integument, and certain muscles The efferent-tubule region of the maxillary gland possessed a distinctive lesion comprised of a group of spirochetes, together with numerous small vesicles, situated in a cave-like indentation of the base of the tubule epithelium. in some instances the basal lamina at a lesion site was clearly discontinuous. High-voltage electron microscopy has now been used to study lesions of the efferent tubule, with the aim of understanding better their three-dimensional structure.Tissue from one maxillary gland of an infected, adult, female brine shrimp was used for HVEM study.

Mitochondrial Reconstructions Based on Serial Thick Sections and HVEM

1975 ◽  
Vol 33 ◽  
pp. 286-287
Author(s):  
Jerome J. Paulin
Keyword(s):  
Imaging Techniques ◽  
Three Dimensional ◽  
Posterior Pole ◽  
Dimensional Structure ◽  
Stereo Imaging ◽  
Thin Sections ◽  
Anatomical Features ◽  
The Past ◽  
Cellular Components ◽  
Mitochondrial Reticulum

Within the past decade it has become apparent that HVEM offers the biologist a means to explore the three-dimensional structure of cells and/or organelles. Stereo-imaging of thick sections (e.g. 0.25-10 μm) not only reveals anatomical features of cellular components, but also reduces errors of interpretation associated with overlap of structures seen in thick sections. Concomitant with stereo-imaging techniques conventional serial Sectioning methods developed with thin sections have been adopted to serial thick sections (≥ 0.25 μm). Three-dimensional reconstructions of the chondriome of several species of trypanosomatid flagellates have been made from tracings of mitochondrial profiles on cellulose acetate sheets. The sheets are flooded with acetone, gluing them together, and the model sawed from the composite and redrawn.The extensive mitochondrial reticulum can be seen in consecutive thick sections of (0.25 μm thick) Crithidia fasciculata (Figs. 1-2). Profiles of the mitochondrion are distinguishable from the anterior apex of the cell (small arrow, Fig. 1) to the posterior pole (small arrow, Fig. 2).

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