scholarly journals A Novel Murine Anti-Lactoferrin Monoclonal Antibody Activates Human Polymorphonuclear Leukocytes through Membrane-Bound Lactoferrin and TLR4

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Xiao-Min Hu ◽  
Yan-Rui Xu ◽  
Ru Yan ◽  
Shu-Liang Sun ◽  
Hong-Liang Dong ◽  
...  
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Iron Homeostasis ◽  
Prognostic Biomarker ◽  
Conformational Epitope ◽  
Health And Disease ◽  
Membrane Bound ◽  
Underlying Mechanisms ◽  
And Function ◽  
Human Polymorphonuclear Leukocytes ◽  
Murine Igg1

Soluble lactoferrin (LTF) is a versatile molecule that not only regulates the iron homeostasis, but also harbors direct microbicidal and immunomodulating abilities in mammalian body fluids. In contrast, little is known about the function of membrane-bound LTF (mbLTF), although its expression on human polymorphonuclear leukocytes (huPMNs) has been reported for decades. Given that LTF/anti-LTF antibodies represent a potential diagnostic/prognostic biomarker and a therapeutic target in patients with immune disorders, we wished, in the present study, to generate a novel human LTF- (huLTF-) specific mAb suitable for detailed analyses on the expression and function of mbLTF as well as for deciphering the underlying mechanisms. By using the traditional hybridoma cell fusion technology, we obtained a murine IgG1 (kappa) mAb, M-860, against huLTF. M-860 recognizes a conformational epitope of huLTF as it binds to natural, but not denatured, huLTF in ELISA. Moreover, M-860 detects mbLTF by FACS and captures endogenous huLTF in total cell lysates of huPMNs. Functionally, M-860 induces the activation of huPMNs partially through TLR4 but independently of phagocytosis. M-860 is thus a powerful tool to analyze the expression and function of human mbLTF, which will further our understanding of the roles of LTF in health and disease.

scholarly journals Polyamine Homeostasis in Development and Disease

2021 ◽  
Vol 9 (2) ◽  
pp. 28
Author(s):  
Shima Nakanishi ◽  
John L. Cleveland
Keyword(s):  
Human Health ◽  
Polyamine Metabolism ◽  
Growth And Survival ◽  
Effective Strategies ◽  
Promote Tumor Growth ◽  
Mammalian Cell Growth ◽  
Health And Disease ◽  
Living Organisms ◽  
Underlying Mechanisms ◽  
And Function

Polycationic polyamines are present in nearly all living organisms and are essential for mammalian cell growth and survival, and for development. These positively charged molecules are involved in a variety of essential biological processes, yet their underlying mechanisms of action are not fully understood. Several studies have shown both beneficial and detrimental effects of polyamines on human health. In cancer, polyamine metabolism is frequently dysregulated, and elevated polyamines have been shown to promote tumor growth and progression, suggesting that targeting polyamines is an attractive strategy for therapeutic intervention. In contrast, polyamines have also been shown to play critical roles in lifespan, cardiac health and in the development and function of the brain. Accordingly, a detailed understanding of mechanisms that control polyamine homeostasis in human health and disease is needed to develop safe and effective strategies for polyamine-targeted therapy.

scholarly journals Iron Homeostasis in the Lungs—A Balance between Health and Disease

2019 ◽  
Vol 12 (1) ◽  
pp. 5 ◽  
Author(s):  
Joana Neves ◽  
Thomas Haider ◽  
Max Gassmann ◽  
Martina U. Muckenthaler
Keyword(s):  
Lung Diseases ◽  
Respiratory Diseases ◽  
Iron Homeostasis ◽  
Current Knowledge ◽  
Chronic Obstructive ◽  
Functional Importance ◽  
Obstructive Pulmonary Disease ◽  
Health And Disease ◽  
Underlying Mechanisms ◽  
Review Current

A strong mechanistic link between the regulation of iron homeostasis and oxygen sensing is evident in the lung, where both systems must be properly controlled to maintain lung function. Imbalances in pulmonary iron homeostasis are frequently associated with respiratory diseases, such as chronic obstructive pulmonary disease and with lung cancer. However, the underlying mechanisms causing alterations in iron levels and the involvement of iron in the development of lung disorders are incompletely understood. Here, we review current knowledge about the regulation of pulmonary iron homeostasis, its functional importance, and the link between dysregulated iron levels and lung diseases. Gaining greater knowledge on how iron contributes to the pathogenesis of these diseases holds promise for future iron-related therapeutic strategies.

scholarly journals Uncovering Membrane-Bound Models of Coagulation Factors by Combined Experimental and Computational Approaches

2021 ◽  
Author(s):  
Y. Zenmei Ohkubo ◽  
Jesper J. Madsen
Keyword(s):  
Coagulation Factors ◽  
The Body ◽  
Computational Studies ◽  
Biological Processes ◽  
Membrane Surfaces ◽  
Health And Disease ◽  
Membrane Bound ◽  
High Space ◽  
Underlying Mechanisms ◽  
Work Done

AbstractIn the life sciences, including hemostasis and thrombosis, methods of structural biology have become indispensable tools for shedding light on underlying mechanisms that govern complex biological processes. Advancements of the relatively young field of computational biology have matured to a point where it is increasingly recognized as trustworthy and useful, in part due to their high space–time resolution that is unparalleled by most experimental techniques to date. In concert with biochemical and biophysical approaches, computational studies have therefore proven time and again in recent years to be key assets in building or suggesting structural models for membrane-bound forms of coagulation factors and their supramolecular complexes on membrane surfaces where they are activated. Such endeavors and the proposed models arising from them are of fundamental importance in describing and understanding the molecular basis of hemostasis under both health and disease conditions. We summarize the body of work done in this important area of research to drive forward both experimental and computational studies toward new discoveries and potential future therapeutic strategies.

scholarly journals Membrane-Bound Meet Membraneless in Health and Disease

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1000 ◽  
Author(s):  
Chujun Zhang ◽  
Catherine Rabouille
Keyword(s):  
Phase Separation ◽  
Membrane Trafficking ◽  
Secretory Pathway ◽  
Dependent Manner ◽  
P Bodies ◽  
Early Secretory Pathway ◽  
Cell Organization ◽  
Health And Disease ◽  
Membrane Bound ◽  
And Function

Membraneless organelles (MLOs) are defined as cellular structures that are not sealed by a lipidic membrane and are shown to form by phase separation. They exist in both the nucleus and the cytoplasm that is also heavily populated by numerous membrane-bound organelles. Even though the name membraneless suggests that MLOs are free of membrane, both membrane and factors regulating membrane trafficking steps are emerging as important components of MLO formation and function. As a result, we name them biocondensates. In this review, we examine the relationships between biocondensates and membrane. First, inhibition of membrane trafficking in the early secretory pathway leads to the formation of biocondensates (P-bodies and Sec bodies). In the same vein, stress granules have a complex relationship with the cyto-nuclear transport machinery. Second, membrane contributes to the regulated formation of phase separation in the cells and we will present examples including clustering at the plasma membrane and at the synapse. Finally, the whole cell appears to transit from an interphase phase-separated state to a mitotic diffuse state in a DYRK3 dependent manner. This firmly establishes a crosstalk between the two types of cell organization that will need to be further explored.

scholarly journals Maternal iron homeostasis: effect on placental development and function

Reproduction ◽  
2020 ◽  
Vol 160 (4) ◽  
pp. R65-R78
Author(s):  
Hannah Roberts ◽  
Stephane L Bourque ◽  
Stephen J Renaud
Keyword(s):  
Iron Deficiency ◽  
Pregnant Women ◽  
Iron Homeostasis ◽  
Current Data ◽  
Placental Development ◽  
Cellular Processes ◽  
Underlying Mechanisms ◽  
Health Complications ◽  
And Function ◽  
Maternal Iron

Iron is an essential mineral that participates in oxygen transport, DNA synthesis and repair, and as a cofactor for various cellular processes. Iron deficiency is the most common nutritional deficiency worldwide. Due to blood volume expansion and demands from the fetal–placental unit, pregnant women are one of the populations most at risk of developing iron deficiency. Iron deficiency during pregnancy poses major health concerns for offspring, including intrauterine growth restriction and long-term health complications. Although the underlying mechanisms remain unclear, maternal iron deficiency may indirectly impair fetal growth through changes in the structure and function of the placenta. Since the placenta forms the interface between mother and baby, understanding how the placenta changes in iron deficiency may yield new diagnostic indices of fetal stress in affected pregnancies, thereby leading to earlier interventions and improved fetal outcomes. In this review, we compile current data on the changes in placental development and function that occur under conditions of maternal iron deficiency, and discuss challenges and perspectives on managing the high incidence of iron deficiency in pregnant women.

Spatial control of actin-based motility through plasmalemmal PtdIns(4,5)P2-rich raft assemblies.

2005 ◽  
Vol 72 ◽  
pp. 119-127 ◽  
Author(s):  
Tamara Golub ◽  
Caroni Pico
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Actin Cytoskeleton ◽  
Lipid Rafts ◽  
Patch Clustering ◽  
Pkc Protein Kinase C ◽  
Membrane Bound ◽  
And Function ◽  
Cytoskeleton Dynamics ◽  
Syndrome Protein

The interactions of cells with their environment involve regulated actin-based motility at defined positions along the cell surface. Sphingolipid- and cholesterol-dependent microdomains (rafts) order proteins at biological membranes, and have been implicated in most signalling processes at the cell surface. Many membrane-bound components that regulate actin cytoskeleton dynamics and cell-surface motility associate with PtdIns(4,5)P2-rich lipid rafts. Although raft integrity is not required for substrate-directed cell spreading, or to initiate signalling for motility, it is a prerequisite for sustained and organized motility. Plasmalemmal rafts redistribute rapidly in response to signals, triggering motility. This process involves the removal of rafts from sites that are not interacting with the substrate, apparently through endocytosis, and a local accumulation at sites of integrin-mediated substrate interactions. PtdIns(4,5)P2-rich lipid rafts can assemble into patches in a process depending on PtdIns(4,5)P2, Cdc42 (cell-division control 42), N-WASP (neural Wiskott-Aldrich syndrome protein) and actin cytoskeleton dynamics. The raft patches are sites of signal-induced actin assembly, and their accumulation locally promotes sustained motility. The patches capture microtubules, which promote patch clustering through PKA (protein kinase A), to steer motility. Raft accumulation at the cell surface, and its coupling to motility are influenced greatly by the expression of intrinsic raft-associated components that associate with the cytosolic leaflet of lipid rafts. Among them, GAP43 (growth-associated protein 43)-like proteins interact with PtdIns(4,5)P2 in a Ca2+/calmodulin and PKC (protein kinase C)-regulated manner, and function as intrinsic determinants of motility and anatomical plasticity. Plasmalemmal PtdIns(4,5)P2-rich raft assemblies thus provide powerful organizational principles for tight spatial and temporal control of signalling in motility.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

“Because every recipient is also a potential patient” – TV Health Programmes in the FRG and the GDR, from the 1960s to the 1980s

Gesnerus ◽  
2019 ◽  
Vol 76 (2) ◽  
pp. 172-191
Author(s):  
Susanne Vollberg
Keyword(s):  
Public Awareness ◽  
West Germany ◽  
Continuous Coverage ◽  
Public Consciousness ◽  
Television Programme ◽  
East German ◽  
Health And Disease ◽  
Media Systems ◽  
The 1960S ◽  
And Function

In the television programme of West Germany from the 1960s to the 1980s, health magazines like Gesundheitsmagazin Praxis [Practice Health Magazine] (produced by ZDF)1 or ARD-Ratgeber: Gesundheit [ARD Health Advisor] played an important role in addressing health and disease as topics of public awareness. With their health magazine Visite [Doctor’s rounds], East German television, too relied on continuous coverage and reporting in the field. On the example of above magazines, this paper will examine the history, design and function of health communication in magazine-type formats. Before the background of the changes in media policy experienced over three decades and the different media systems in the then two Germanys, it will discuss the question of whether television was able to move health relevant topics and issues into public consciousness.

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