scholarly journals Alpha-2-Macroglobulin, a Hypochlorite-Regulated Chaperone and Immune System Modulator

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Jordan H. Cater ◽  
Mark R. Wilson ◽  
Amy R. Wyatt
Keyword(s):  
Growth Factors ◽  
Immune System ◽  
Synovial Fluid ◽  
Amyloid Beta ◽  
Broad Spectrum ◽  
Cerebral Spinal Fluid ◽  
Interstitial Fluid ◽  
Biological Fluids ◽  
Biological Processes ◽  
Ancient Proteins

Alpha-macroglobulins are ancient proteins that include monomeric, dimeric, and tetrameric family members. In humans, and many other mammals, the predominant alpha-macroglobulin is alpha-2-macroglobulin (α2M), a tetrameric protein that is constitutively abundant in biological fluids (e.g., blood plasma, cerebral spinal fluid, synovial fluid, ocular fluid, and interstitial fluid).α2M is best known for its remarkable ability to inhibit a broad spectrum of proteases, but the full gamut of its activities affects diverse biological processes. For example,α2M can stabilise and facilitate the clearance of the Alzheimer’s disease-associated amyloid beta (Aβ) peptide. Additionally,α2M can influence the signalling of cytokines and growth factors including neurotrophins. The results of several studies support the idea that the functions ofα2M are uniquely regulated by hypochlorite, an oxidant that is generated during inflammation, which induces the nativeα2M tetramer to dissociate into dimers. This review will discuss the evidence for hypochlorite-induced regulation ofα2M and the possible implications of this in neuroinflammation and neurodegeneration.

Fisiopatología de la hidrocefália idiopática de presión normal (parte 3): sistemaa glinfático

2016 ◽  
Vol 21 (2) ◽  
pp. 28-37
Author(s):  
Oscar Solís-Salgado ◽  
José Luis López-Payares ◽  
Mauricio Ayala-González
Keyword(s):  
Amyloid Beta ◽  
Interstitial Fluid ◽  
Amyloid Β ◽  
Bulk Flow ◽  
Polyethylene Glycols ◽  
Brain Interstitial Fluid ◽  
El Sistema ◽  
Arterial Pulsation ◽  
The Brain

Las vías de drenaje solutos del sistema nervioso central (SNC) participan en el recambio de liquido intersticial con el líquido cefalorraquídeo (LIT-LCR), generando un estado de homeostasis. Las alteraciones dentro de este sistema homeostático afectará la eliminación de solutos del espacio intersticial (EIT) como el péptido βa y proteína tau, los cuales son sustancias neurotóxicas para el SNC. Se han utilizado técnicas experimentales para poder analizar el intercambio LIT-LCR, las cuales revelan que este intercambio tiene una estructura bien organizada. La eliminación de solutos del SNC no tiene una estructura anatómica propiamente, se han descubierto vías de eliminación de solutos a través de marcadores florecentes en el espacio subaracnoideo, cisternas de la base y sistema ventricular que nos permiten observar una serie de vías ampliamente distribuidas en el cerebro. El LCR muestra que tiene una función linfática debido a su recambio con el LIT a lo largo de rutas paravasculares. Estos espacios que rodean la superficie arterial así como los espacios de Virchow-Robin y el pie astrocitico junto con la AQP-4, facilitan la entrada de LCR para-arterial y el aclaramiento de LIT para-venoso dentro del cerebro. El flujo y dirección que toma el LCR por estas estructuras, es conducido por la pulsación arterial. Esta función será la que finalmente llevara a la eliminación de estas sustancias neurotóxicas. En base a la dependencia de este flujo para la eliminación de sustancias se propone que el sistema sea llamado “ la Vía Glinfática”. La bibliografía así como las limitaciones que se encuentran en esta revisión están dadas por la metodología de búsqueda que ha sido realizada principalmente en PubMed utilizando los siguientes términos Mesh: Cerebral Arterial Pulsation, the brain via paravascular, drainage of amyloid-beta, bulk flow of brain interstitial fluid, radiolabeled polyethylene glycols and albumin, amyloid-β, the perivascular astroglial sheath, Brain Glymphatic Transport.

Control of Interstitial Fluid Homeostasis: Roles of Growth Factors and Integrins

2008 ◽  
pp. 105-115 ◽  
Author(s):  
Kristofer Rubin ◽  
Åsa Lidén ◽  
Tijs van Wieringen ◽  
Rolf K. Reed
Keyword(s):  
Growth Factors ◽  
Interstitial Fluid ◽  
Fluid Homeostasis

scholarly journals Synovial Fluid Profile Dictates Nanopracticle Uptake into Cartilage- Implications of the Protein Corona for Novel Arthitis Treatments

2021 ◽  
Author(s):  
Ula von Mentzer ◽  
Tilia Selldén ◽  
LOISE Råberg ◽  
Gizem Erensoy ◽  
Anna-Karin Hultgård-Ekwall ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Synovial Fluid ◽  
Electrostatic Interactions ◽  
Fetal Calf Serum ◽  
Biological Fluids ◽  
Calf Serum ◽  
Protein Corona ◽  
Drug Delivery Vehicles ◽  
Drug Concentrations

<div>Intra-articular drug delivery strategies aiming to deliver drugs in diseases affected by cartilage-related issues are using electrostatic interactions to penetrate the dense cartilage matrix. This enables delivery of sufficient drug concentrations to the chondrocytes to mediate the desired therapeutic effect. As it is well known that size and charge of nanoparticles affects its interactions with the surrounding biological fluids, where proteins adsorb to the NP surface, resulting in a protein corona. There are, however, no studies investigating how the formed protein coronas affect cartilage uptake and subsequent cellular uptake, nor how they affect other cells present in the synovium of such diseases. Here, we explore the differences between the protein coronas that form when NP are incubated in synovial fluid from osteoarthritic and rheumatoid arthritis patients and compare this to results obtained using fetal calf serum (FCS), as guide for researchers working on joint drug delivery. We demonstrate that the protein corona indeed affects the uptake into cartilage, where there are major differences between the model proteins in fetal calf serum, as compared to synovial fluid from rheumatoid arthritis patients as well as osteoarthritis patients. The data suggests that when developing drug delivery vehicles for joint diseases that leverages electrostatic interactions and size, the interactions with proteins in the biological milieu is highly relevant to consider.</div>

Roles of Secreted Phospholipases A2 in the Mammalian Immune System

2014 ◽  
Vol 21 (12) ◽  
pp. 1201-1208
Author(s):  
Igor Krizaj
Keyword(s):  
Immune System ◽  
Acute Inflammation ◽  
The Body ◽  
Innate Immune ◽  
Future Research ◽  
Biological Processes ◽  
Phospholipases A2 ◽  
Protective Reaction ◽  
Severe Pathology ◽  
Mammalian Immune System

Secreted phospholipase A2 (sPLA2) molecules constitute a family of proteins that are involved functionally in many biological processes. In particular, they participate in diverse pathophysiological settings as enzymes that release free fatty acids and lysophospholipids from phospholipids in biological membranes, or as ligands for various cellular receptors. In this review the confirmed or expected functions of sPLA2s in the mammalian immune system are surveyed. Some of the twelve mammalian sPLA2 molecules constitute part of the so-called innate immune system by virtue of their antibacterial, antiviral and antifungal activities. They are also involved in acute inflammation, a protective reaction of the body to infection or injury. The acute inflammation sometimes escapes regulation, becomes chronic and can evolve into a severe pathology. One or more types of sPLA2 are involved in asthma, rheumatoid arthritis, sepsis, atherosclerosis, myocardial infarction, Crohn’s disease, ulcerative colitis and cancer. sPLA2s are thus important therapeutic targets as well as biotherapeutic molecules. Improving the selectivity of inhibitors of sPLA2s to be able to target a particular sPLA2 could therefore be one of the most important tasks for future research.

scholarly journals Platelet Extracellular Vesicles

2020 ◽  
Author(s):  
Florian Puhm ◽  
Eric Boilard ◽  
Kellie R. Machlus
Keyword(s):  
Bone Marrow ◽  
Synovial Fluid ◽  
Nucleic Acids ◽  
Extracellular Vesicles ◽  
Cell Communication ◽  
Biological Processes ◽  
Vascular Integrity ◽  
Pathological Conditions ◽  
Broad Array

Extracellular vesicles (EVs) are a means of cell-to-cell communication and can facilitate the exchange of a broad array of molecules between adjacent or distant cells. Platelets are anucleate cells derived from megakaryocytes and are primarily known for their role in maintaining hemostasis and vascular integrity. Upon activation by a variety of agonists, platelets readily generate EVs, which were initially identified as procoagulant particles. However, as both platelets and their EVs are abundant in blood, the role of platelet EVs in hemostasis may be redundant. Moreover, findings have challenged the significance of platelet-derived EVs in coagulation. Looking beyond hemostasis, platelet EV cargo is incredibly diverse and can include lipids, proteins, nucleic acids, and organelles involved in numerous other biological processes. Furthermore, while platelets cannot cross tissue barriers, their EVs can enter lymph, bone marrow, and synovial fluid. This allows for the transfer of platelet-derived content to cellular recipients and organs inaccessible to platelets. This review highlights the importance of platelet-derived EVs in physiological and pathological conditions beyond hemostasis.

Electrochemistry of Alzheimer Disease Amyloid Beta Peptides

2018 ◽  
Vol 25 (33) ◽  
pp. 4066-4083 ◽  
Author(s):  
Ana-Maria Chiorcea-Paquim ◽  
Teodor Adrian Enache ◽  
Ana Maria Oliveira-Brett
Keyword(s):  
Amino Acid ◽  
Amyloid Beta ◽  
Biological Fluids ◽  
Electron Transfer Reaction ◽  
Random Coil ◽  
Sequence Length ◽  
Dependent Manner ◽  
Aβ Peptide ◽  
Aβ Peptides ◽  
Α Helix

Alzheimer’s disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity. This review discusses the recent advances on the Aβ peptides electrochemical characterization. The Aβ peptides oxidation at a glassy carbon electrode occurs in one or two steps, depending on the amino acid sequence, length and content. The first electron transfer reaction corresponds to the tyrosine Tyr10 amino acid residue oxidation, and the second to all three histidine (His6, His13 and His14) and one methionine (Met35) amino acid residues. The Aβ peptides aggregation and amyloid fibril formation are electrochemically detected via the electroactive amino acids oxidation peak currents decrease that occurs in a time dependent manner. The Aβ peptides redox behaviour is correlated with changes in the adsorption morphology from initially random coiled structures, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to aggregates, protofibrils and two types of fibrils, corresponding to the Aβ peptides in a β-sheet configuration, observed by atomic force microscopy. Electrochemical studies of Aβ peptides aggregation, mediated by the interaction with metal ions, particularly zinc, copper and iron, and different methodologies concerning the detection of Aβ peptide biomarkers of AD in biological fluids, using electrochemical biosensors, are also discussed.

scholarly journals Cytokine Interactions with Epithelium

1996 ◽  
Vol 10 (5) ◽  
pp. 323-328 ◽  
Author(s):  
Kim E Barrett
Keyword(s):  
Growth Factors ◽  
Immune System ◽  
Adhesion Molecules ◽  
Inflammatory Mediators ◽  
Intestinal Inflammation ◽  
Current Knowledge ◽  
Cell Types ◽  
Epithelial Damage ◽  
Intracellular Messengers ◽  
Cytokine Interactions

Cytokines are a family of proteins that serve as intracellular messengers within the immune system and as growth factors for several cell types. Recent studies indicate that intestinal inflammation is accompanied by increases in a wide variety of cytokines and growth factors. Current knowledge in the area of cytokine-epithelial interactions, with particular reference to the involvement of such interactions in intestinal inflammation, is reviewed. Topics include epithelial functions subject to modulation by cytokines; effects of cytokines on epithelial damage, restitution and proliferation; effects of cytokines on the ability of the epithelium to express immune accessory and adhesion molecules; and effects of cytokines on the production of inflammatory mediators by the epithelium.

IMMUNOASSAY FOR MEASURING THE HEPARIN-BINDING GROWTH FACTORS HARP AND MK IN BIOLOGICAL FLUIDS

2002 ◽  
Vol 23 (1) ◽  
pp. 33-48 ◽  
Author(s):  
Patrick Soulié ◽  
Mélanie Héroult ◽  
Isabelle Bernard ◽  
Marie-Emmanuelle Kerros ◽  
Pierre Emmanuel Milhiet ◽  
...  
Keyword(s):  
Growth Factors ◽  
Biological Fluids ◽  
Heparin Binding ◽  
Heparin Binding Growth Factors
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