scholarly journals Microparticles That Form Immune Complexes as Modulatory Structures in Autoimmune Responses

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Catalina Burbano ◽  
Mauricio Rojas ◽  
Gloria Vásquez ◽  
Diana Castaño
Keyword(s):  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Cell Activation ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Functional Characterization ◽  
Target Cells ◽  
Proinflammatory Response ◽  
Extracellular Milieu

Microparticles (MPs) are induced during apoptosis, cell activation, and even “spontaneous” release. Initially MPs were considered to be inert cellular products with no biological function. However, an extensive research and functional characterization have shown that the molecular composition and the effects of MPs depend upon the cellular background and the mechanism inducing them. They possess a wide spectrum of biological effects on intercellular communication by transferring different molecules able to modulate other cells. MPs interact with their target cells through different mechanisms: membrane fusion, macropinocytosis, and receptor-mediated endocytosis. However, when MPs remain in the extracellular milieu, they undergo modifications such as citrullination, glycosylation, and partial proteolysis, among others, becoming a source of neoantigens. In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), reports indicated elevated levels of MPs with different composition, content, and effects compared with those isolated from healthy individuals. MPs can also form immune complexes amplifying the proinflammatory response and tissue damage. Their early detection and characterization could facilitate an appropriate diagnosis optimizing the pharmacological strategies, in different diseases including cancer, infection, and autoimmunity. This review focuses on the current knowledge about MPs and their involvement in the immunopathogenesis of SLE and RA.

New targeted therapies for treatment of thrombosis in antiphospholipid syndrome

2007 ◽  
Vol 9 (30) ◽  
pp. 1-15 ◽  
Author(s):  
Silvia S. Pierangeli ◽  
Mariano E. Vega-Ostertag ◽  
Emilio B. González
Keyword(s):  
Antiphospholipid Syndrome ◽  
Targeted Therapies ◽  
Lupus Erythematosus ◽  
Pregnancy Loss ◽  
Cell Activation ◽  
Clinical Manifestations ◽  
Target Cells ◽  
Endothelial Cell Activation ◽  
In Vivo Models

Antiphospholipid (aPL) antibodies (Abs) are associated with thrombosis and pregnancy loss in antiphospholipid syndrome (APS), a disorder initially characterised in patients with systemic lupus erythematosus (SLE) but now known to occur in the absence of other autoimmune disease. There is strong evidence that aPL Abs are pathogenic in vivo, from studies of animal models of thrombosis, endothelial cell activation and pregnancy loss. In recent years, progress has been made in characterising the molecular basis of this pathogenicity, which includes direct effects on platelets, endothelial cells and monocytes as well as activation of complement. This review summarises the clinical manifestations of APS and current modalities of treatment, and explains recent advances in understanding the molecular events triggered by aPL Abs on target cells in coagulation pathways as well as effects of aPL Abs on complement activation. Based on this information and on additional scientific evidence using in vitro and in vivo models, new potential targeted therapies for treatment and/or prevention of thrombosis in APS are proposed and discussed.

scholarly journals Toll-like Receptor 9–Dependent and –Independent Dendritic Cell Activation by Chromatin–Immunoglobulin G Complexes

2004 ◽  
Vol 199 (12) ◽  
pp. 1631-1640 ◽  
Author(s):  
Melissa W. Boulé ◽  
Courtney Broughton ◽  
Fabienne Mackay ◽  
Shizuo Akira ◽  
Ann Marshak-Rothstein ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Cell Activation ◽  
Critical Role ◽  
Adaptive Immune Response ◽  
Foreign Protein ◽  
Interleukin 12 ◽  
Toll Like Receptor ◽  
Dendritic Cell Activation

Dendritic cell (DC) activation by nucleic acid–containing immunoglobulin (Ig)G complexes has been implicated in systemic lupus erythematosus (SLE) pathogenesis. However, the mechanisms responsible for activation and subsequent disease induction are not completely understood. Here we show that murine DCs are much more effectively activated by immune complexes that contain IgG bound to chromatin than by immune complexes that contain foreign protein. Activation by these chromatin immune complexes occurs by two distinct pathways. One pathway involves dual engagement of the Fc receptor FcγRIII and Toll-like receptor (TLR)9, whereas the other is TLR9 independent. Furthermore, there is a characteristic cytokine profile elicited by the chromatin immune complexes that distinguishes this response from that of conventional TLR ligands, notably the induction of BAFF and the lack of induction of interleukin 12. The data establish a critical role for self-antigen in DC activation and explain how the innate immune system might drive the adaptive immune response in SLE.

scholarly journals Acquired White Oral Lesions with Specific Patterns: Oral Lichen Planus and Lupus Erythematosus

2021 ◽  
pp. 2021074
Author(s):  
Marco Manfredini ◽  
Gioia Pedroni ◽  
Laura Bigi ◽  
Roberto Apponi ◽  
Alberto Murri dello Iago ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Current Knowledge ◽  
Wide Spectrum ◽  
Case Reports ◽  
Case Series ◽  
Specific Pattern ◽  
Special Pattern ◽  
Lichenoid Reactions ◽  
Immunomodulatory Therapies ◽  
Oral Lichen

Background: Diagnosis of oral white lesions might be challenging. These lesions represent a wide spectrum of diseases with different etiology and prognosis. Oral white lesions can be categorized into two major groups, congenital and acquired, according to their development, and in four subgroups: lesions which can be scraped off or not and lesions with special pattern or not. Objectives: The aim of this manuscript is to review, from diagnosis to treatment, the current knowledge on oral white lesions with specific pattern. Methods: A review on oral white lesions with specific pattern was conducted on PubMed and Scopus from inception to January 2021. Results: Among acquired lesions with specific pattern two clinical entities are mostly represented: Oral lichenoid reactions and Lupus erythematosus. The etiology of both diseases is still not known but their pathogenesis is mainly immunological. At present the mucoscopic features of those disease have been described only in few case reports or case series. Immunomodulatory therapies are often the agents of choice for their treatment. Conclusions: The collaboration of dermatologists and dentists as a team is important for early diagnoses and effective treatments. Mucoscopy is a promising technique which may reveal important features for the differentiation of OLP and LE oral white lesions.

scholarly journals Mutations and polymorphisms in FSH receptor: functional implications in human reproduction

Reproduction ◽  
2013 ◽  
Vol 146 (6) ◽  
pp. R235-R248 ◽  
Author(s):  
Swapna S Desai ◽  
Binita Sur Roy ◽  
Smita D Mahale
Keyword(s):  
Cell Function ◽  
Current Knowledge ◽  
Functional Characterization ◽  
Genetic Alterations ◽  
Human Reproduction ◽  
Receptor Interaction ◽  
Optimum Dose ◽  
Individual Treatment ◽  
Target Cells ◽  
Fsh Receptor

FSH brings about its physiological actions by activating a specific receptor located on target cells. Normal functioning of the FSH receptor (FSHR) is crucial for follicular development and estradiol production in females and for the regulation of Sertoli cell function and spermatogenesis in males. In the last two decades, the number of inactivating and activating mutations, single nucleotide polymorphisms, and spliced variants of FSHR gene has been identified in selected infertile cases. Information on genotype–phenotype correlation and in vitro functional characterization of the mutants has helped in understanding the possible genetic cause for female infertility in affected individuals. The information is also being used to dissect various extracellular and intracellular events involved in hormone–receptor interaction by studying the differences in the properties of the mutant receptor when compared with WT receptor. Studies on polymorphisms in the FSHR gene have shown variability in clinical outcome among women treated with FSH. These observations are being explored to develop molecular markers to predict the optimum dose of FSH required for controlled ovarian hyperstimulation. Pharmacogenetics is an emerging field in this area that aims at designing individual treatment protocols for reproductive abnormalities based on FSHR gene polymorphisms. The present review discusses the current knowledge of various genetic alterations in FSHR and their impact on receptor function in the female reproductive system.

scholarly journals Study on the Role of Vitamin D in Systemic Lupus Erythematosus

2021 ◽  
Vol 4 (1) ◽  
pp. 23
Author(s):  
Jiadian Wang ◽  
Muzi Cui ◽  
Siyi Wang ◽  
Xiao Xue ◽  
Kerong Ren ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Vitamin D ◽  
Lupus Erythematosus ◽  
Biological Effects ◽  
Research Progress ◽  
Target Cells ◽  
Systemic Lupus ◽  
Vitamin D Receptors

Vitamin D is a hormone precursor with multiple biological effects. It binds to vitamin D receptors on target cells. It is an important participant in the metabolism of calcium and phosphorus in vivo. It is closely related to cell cycle, cell proliferation, differentiation, apoptosis, signal transduction and immune regulation. Its role in the treatment of infection, tumor and even immune diseases has been gradually recognized and studied. Patients with systemic lupus erythematosus generally have decreased levels of active vitamin D, and low levels of vitamin D are associated with disease occurrence, disease activity and complications. In the past ten years, a large number of studies have been carried out on it globally to explore the role of vitamin D in the occurrence and development of systemic lupus erythematosus. This paper summarizes its recent research progress.

Coagulation and Fibrinolysis Study in Systemic Lupus erythematosus: Haematological, Urinary and Tissue Parameters

1981 ◽  
Vol 46 (03) ◽  
pp. 575-580 ◽  
Author(s):  
P Stratta ◽  
C Canavese ◽  
P Valmaggia ◽  
M Rotunno ◽  
E Levi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Acute Stage ◽  
Systemic Lupus ◽  
Immunological Activity ◽  
Coagulation Abnormalities ◽  
Coagulation And Fibrinolysis

SummaryHaematochemical, urinary and tissue parameters were examined in the elaboration of the coagulation and fibrinolysis profile in 33 cases of systemic lupus erythematosus in different stages of the disease. Coagulation abnormalities varied from hypo- to hyper-coagulabitity, these being often associated in the same patient, either simultaneously or at different stages of the disease. Activation of coagulation, closely related to the immunological activity of the disease, was present in 80% cases in the acute stage, and 36% of those in the remission stage. The lupus-like anticoagulant was not much involved, and platelets were the prime figures in the haemostatic abnormalities of lupus, those being the preferred target of direct antibody activities, or possibly of immune complexes as well. Activation of the coagulatory cascade is not uncommonly accompanied by a thrombophilic tendency coupled with signs of consumption, this being the expression of a continuously stimulated haemostatic balance.

Studies on the Binding of Proteins to the Human Platelet Surface: Relation to Platelet Activation

1985 ◽  
Vol 53 (03) ◽  
pp. 360-365 ◽  
Author(s):  
Gerhard K M Endresen ◽  
Øystein Førre
Keyword(s):  
Platelet Aggregation ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Immunofluorescent Staining ◽  
Induce Platelet Aggregation ◽  
Platelet Surface ◽  
Platelet Aggregometry ◽  
Surface Staining ◽  
Alpha1 Antitrypsin ◽  
Induced Aggregation

SummarySeveral antibody fractions and sera from patients with rheumatoid arthritis, systemic lupus erythematosus and chronic idiopathic thrombocytopenic purpura were examined for their ability to bind to normal platelets using immunofluorescent staining techniques. Platelet aggregometry was used to study the activating capacity of the samples.Both C1q, C1s, C1 inactivator, fibrinogen, factor VIII-related antigen, alpha1-acid glycoprotein, alpha1-antitrypsin, beta2-micro- globulin and isoantigens A and B, as well as fibronectin and plasminogen were found on the platelet surface. Only antibodies to C1q, C1s and beta2-microglobulin were able to induce platelet aggregation. Sera containing immune complexes or platelet autoantibodies revealed positive surface staining for IgG, or for IgG and IgM. These sera also induced aggregation of platelets. Sera not containing immune complexes or autoantibodies gave negative staining and aggregation results. Thus, only some of the ligand receptor interactions were able to induce platelet aggregation.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

Gut Mycobiota and Fungal Metabolites in Human Homeostasis

2018 ◽  
Vol 20 (2) ◽  
pp. 232-240 ◽  
Author(s):  
Izabella Mogilnicka ◽  
Marcin Ufnal
Keyword(s):  
Wide Spectrum ◽  
Biological Effects ◽  
Fungal Species ◽  
Fungal Metabolites ◽  
Human Gut ◽  
Fecal Transplantation ◽  
Bacterial Microbiota ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:Accumulating evidence suggests that microbiota play an important role in host’s homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.Methods:We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.Results:Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.Conclusion:The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.

Cucurbitacins as Anticancer Agents: A Patent Review

2019 ◽  
Vol 14 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Hidayat Hussain ◽  
Ivan R. Green ◽  
Muhammad Saleem ◽  
Khanzadi F. Khattak ◽  
Muhammad Irshad ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Natural Sources ◽  
Oh Groups ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

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