scholarly journals Cathelicidin – Its Structure, Function and the Role in Autoimmune Diseases

2014 ◽  
Vol 4 (2) ◽  
pp. 83-96 ◽  
Author(s):  
Magdalena Polcyn-Adamczak ◽  
Zofia I. Niemir
Keyword(s):  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Helical Structure ◽  
Threshold Concentration ◽  
Amino Acid Residues ◽  
Phospholipid Membrane ◽  
Gram Positive Bacteria ◽  
Extracellular Traps ◽  
Inflammatory Processes

Summary Antimicrobial peptides are widely distributed in nature, and they are found in both Prokaryotes and Eukaryotes. Due to their characteristics, structure, functions and mode of action, they are divided into several groups. The only member of this family occurring in humans is cathelicidin - LL-37. It is produced as an inactive hCAP18 propeptide. The propeptide’s C-terminal fragment becomes a mature peptide subsequently to its enzymatic cleavage. LL-37 contains 37-amino acid residues, folds into α-helical structure and has amphipathic properties. Cathelicidin mechanism of action consists in the binding of LL-37 to the bacterial phospholipid membrane until a threshold concentration is reached, followed by the cytoplasm disintegration and leakage, and, finally, cell death. The peptide is expressed in several cells, for instance in the epithelial cells of testis, keratinocytes in the skin, leukocytes, monocytes, neutrophils, as well as T, B, and NK cells. Cathelicidin is a multifunctional molecule. It can serve as a mediator in inflammatory processes and/or as a natural antibiotic against Gram-negative and Gram-positive bacteria, viruses, and fungi. It is chemotactic for mononuclear cells, neutrophils, eosinophils, mast cells and T lymphocytes. LL-37 induces expression of chemokines, neutralises endotoxins, stimulates angiogenesis and apoptosis, as well as it boosts wound healing. Recent data have revealed an important role of LL-37 in the pathogenesis of systemic lupus erythematosus due to an impaired degradation of components in the neutrophil extracellular traps

Low Density Granulocytes in Patients after Allogeneic Hematopoietic Stem Cells Transplantation (allo-HSCT): A Distinct Class of Neutrophils in Systemic Alloimmunity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4614-4614
Author(s):  
Ekaterina Mikhaltsova ◽  
Valeri G. Savchenko ◽  
Larisa A. Kuzmina ◽  
Mikhail Drokov ◽  
Vera Vasilyeva ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Human Peripheral Blood ◽  
Unrelated Donor ◽  
Low Density ◽  
Hematopoietic Stem

Abstract Introduction It's generally considered that all alloimmune process such as acute graft-versus host disease (aGVHD) after allo-HSCT are mostly controlled by lymphocytes. The role of neutrophils in systemic alloimmunity after allo-HSCT is still illusive. In 1987 a distinct subset of proinflammatory, low-density granulocytes (LDGs) isolated from the peripheral blood mononuclear cell fractions of patients with system lupus erythematosus has been described. There is no LDG's in healthy donors. While the origin and role of LDGs still needs to be fully characterized, we try to describe this population in patients with hematological malignancies after allo-HSCT Patients and methods. Peripheral blood samples were collected in EDTA-tubes before allo-HSCT, on day +30,+60,+90 after allo-HSCT and at day of aGVHD from 47 patients with hematological malignancies (AML=22, ALL n=17, LPD=3, MDS =2; CML=2; 17 with active disease, 30 - in CR) after allo-HSCT (from matched unrelated donor n=34, from matched related donor n=13; MAC = 13, RIC=34). Isolation of mononuclear cells from human peripheral blood was made by standard protocol using Lympholyte®-M Cell Separation Media (Cedarlane Labs). The anti-CD66b-PE (Biolegend, USA) antibodies and FSC/SSC were used to determine LDGs cells as FSChigh \SSChigh \CD66b+. 100000 of cells were analyzed on a BD FACSCanto II (Becton Dickinson, USA). Results. Results of blood evaluation of 47 patients with hematological malignancies, whose blood was examined after allo-HSCT presented in table 1. Conclusion Despite the fact that we don't get significant differences. LDG's detection in allo-HSCT patients need further investigation. Table 1. Incidence of LDG after allo-HSCT in patients with and without aGVHD Table 1. Incidence of LDG after allo-HSCT in patients with and without aGVHD Disclosures No relevant conflicts of interest to declare.

scholarly journals The Role of Mesenchymal Stem Cells in Decreasing Interleukin-12 Human Systemic Lupus Erythematosus

2020 ◽  
Vol 8 (A) ◽  
pp. 787-792
Author(s):  
Delfitri Munir ◽  
Rodiah Rahmawaty Lubis ◽  
Dewi Masyithah Darlan ◽  
Agung Putra ◽  
Iffan Allif
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Interleukin 12 ◽  
Control Group ◽  
Systemic Lupus ◽  
Control Group Design

BACKGROUND: Systemic lupus erythematosus (SLE) disease is characterized by a loss of self-tolerance leading to a local tissue inflammation up to a massive systemic organ-spesific inflammation. Mesenchymal stem cells (MSCs) present immunomodulatory properties to control the over-activating immune responses in SLE through several mechanisms. However, the capability of MSCs to decrease interleukin (IL)-12 production in in vitro remains unclear. AIM: The aim of this study was to investigate the role of MSCs in decreasing the level of IL-12 derived from peripheral blood mononuclear cells (PBMCs) of SLE patients. METHODS: This study used a post-test control group design using a coculture of PBMCs from SLE and healthy patients with MSCs as the subjects. This study included five groups: sham (Sh), control (C), and treatment groups (T) treated by a co-culture MSCs with PBMCs at ratio dose of 1:1 (T1), 1:25 (T2), and 1:50 (T3), respectively, for 72 hours of incubation. The IL-12 levels was analysed by cytometric bead array (CBA) of flow cytometry. RESULTS: This study showed a significant decrease of IL-12 levels (p < 0.05) in T1 and T2 after 72 hours incubation of co-culture MSCs with PBMCs from SLE patient. CONCLUSION: MSCs could decrease the level of IL-12 in PBMCs of human SLE to control the inflammation of SLE disease.

European Forum on Antiphospholipid Antibodies: research in progress

Lupus ◽  
2009 ◽  
Vol 18 (10) ◽  
pp. 924-929 ◽  
Author(s):  
PL Meroni ◽  
A Tincani ◽  
ME Alarcón-Riquelme ◽  
Y Shoenfeld ◽  
MO Borghi
Keyword(s):  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Infectious Agents ◽  
Research Projects ◽  
Epitope Specificity ◽  
European Forum ◽  
New Information ◽  
Inflammatory Processes ◽  
Binding Avidity

The research projects of the European Forum on Antiphospholipid Antibodies are representative of how dynamic is this area of investigation. The present review is focused on the most recent projects of the Forum on the aetiopathogenic aspects of the antiphospholipid syndrome (APS). Studies on the genetic background of the APS are ongoing in order to better define the proximity between APS and full-blown systemic lupus erythematosus. However, the analysis of the polymorphisms of genes coding for inflammatory mediators may offer new information on the role of inflammatory processes in triggering thrombotic events as well as the whole susceptibility for developing the vascular manifestations. A systematic and wide detection of serological markers of infectious processes will give new insight on the role of infectious agents in favouring autoimmunity in APS. Owing to the well-known role of vitamin D3 defect in autoimmune disease, the detection of vitamin plasma levels in APS patients will offer the rationale for a possible therapeutic supplementation. Additional projects are aimed to better characterize the diagnostic/prognostic value of antiphospholipid antibodies (aPL) by defining their epitope specificity and binding avidity. Pregnancy complications represent the obstetric side of APS. Research projects are focussed on the role of complement activation in placenta damage and on the potential ability of aPL to affect the fertility. Finally, a study has been planned in order to draw definitive conclusions on the associations between aPL and atherosclerosis.

scholarly journals The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate-5-lipoxygenase, but not the release of cellular arachidonate.

1989 ◽  
Vol 170 (3) ◽  
pp. 847-863 ◽  
Author(s):  
J M Schröder
Keyword(s):  
Arachidonic Acid ◽  
Human Neutrophil ◽  
Time Course ◽  
Mononuclear Cells ◽  
Interleukin 8 ◽  
Maximal Concentration ◽  
Inflammatory Processes ◽  
Ltb4 Production ◽  
Rapid Activation

LPS and mitogen-stimulated mononuclear cells secrete a cytokine, which is able to activate the PMNL-arachidonate-5-lipoxygenase. This cytokine has been proven to be identical with the recently characterized novel neutrophil-activating peptide NAP/IL-8. NAP/IL-8 is able to activate human PMNL for release of LTB4, omega-oxidized LTB4, and 5-HETE in the presence of exogenous AA. Half-maximal concentration of NAP/IL-8 for release of LTB4 has been found to be near 4 x 10(-8) mol/liter. Time course studies revealed rapid activation of PMNL, with maximal release of LTB4 within the first 10 min with a decline up to 40 min. High amounts of omega-oxidized LTB4 were detected up to that time. Significant amounts of AA-5-LO-products can be detected only when PMNL were stimulated with NAP/IL-8 in the presence of exogenous AA. The concentration of AA necessary for half-maximal LTB4 release has been found to be 3 x 10(-6) mol/liter. In the presence of 8 x 10(-9) mol/liter [3H]AA, NAP/IL-8 (10(-9) to 10(-7) mol/liter) did not induce the production of LTB4, omega-oxidized LTB4, or 5-HETE. In addition, PMNL prelabeled with [3H]AA did not release either [3H]AA or 5-lipoxygenase metabolites when stimulated with NAP/IL-8 (10(-9) to 10(-7) mol/liter), indicating that NAP/IL-8 apparently does not activate cellular phospholipases/diacylglycerol-lipases. Apart from FMLP, C5a, and PAF NAP/IL-8 is the fourth clearly characterized neutrophil chemotaxin able to activate the PMNL-5-lipoxygenase. The detection of large amounts of NAP/IL-8, arachidonic acid, as well as LTB4-like material, in lesional material of patients with psoriasis points towards a possibly important role of NAP/IL-8 in amplifying inflammatory processes by induction of LTB4-production.

Role of neutrophils in equine asthma

2018 ◽  
Vol 19 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Benjamin Uberti ◽  
Gabriel Morán
Keyword(s):  
Tissue Injury ◽  
Oxygen Species ◽  
Cytokine Release ◽  
Extracellular Traps ◽  
Early Responder ◽  
Inflammatory Processes ◽  
Equine Asthma ◽  
Pulmonary Remodeling ◽  
Neutrophil Survival

AbstractNeutrophilic bronchiolitis is the primary lesion in asthma-affected horses. Neutrophils are key actors in host defense, migrating toward sites of inflammation and infection, where they act as early responder cells toward external insults. However, neutrophils can also mediate tissue damage in various non-infectious inflammatory processes. Within the airways, these cells likely contribute to bronchoconstriction, mucus hypersecretion, and pulmonary remodeling by releasing pro-inflammatory mediators, including the cytokines interleukin (IL)-8 and IL-17, neutrophil elastase, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). The mechanisms that regulate neutrophil functions in the tissues are complex and incompletely understood. Therefore, the inflammatory activity of neutrophils must be regulated with exquisite precision and timing, a task achieved through a complex network of mechanisms that regulates neutrophil survival. The discovery and development of compounds that can help regulate ROS, NET formation, cytokine release, and clearance would be highly beneficial in the design of therapies for this disease in horses. In this review, neutrophil functions during inflammation will be discussed followed by a discussion of their contribution to airway tissue injury in equine asthma.

Circular RNAS: novel biomarkers of disease activity in systemic lupus erythematosus?

2019 ◽  
Vol 133 (9) ◽  
pp. 1049-1052 ◽  
Author(s):  
Raquel Cortes ◽  
Maria J. Forner
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Circular Rnas ◽  
Systemic Lupus ◽  
Competitive Endogenous Rnas ◽  
Potential Biomarker ◽  
Inflammatory Processes

Abstract Circular RNAs (circRNAs) are a class of non-coding RNAs that regulate gene expression by acting as competitive endogenous RNAs (ceRNAs) and modulating gene transcription. Several studies support the implication of circRNAs in a variety of human diseases, but research on the role of circRNAs in systemic lupus erythematosus (SLE) is lacking. In a study recently published in Clinical Science (2018), Zhang et al. identified hsa_circ_0012919 as a potential biomarker of disease activity in SLE patients. The authors observed different circRNA expression between SLE patients and healthy controls, an association with clinical variables and with the abnormal DNA methylation present in SLE CD4+ T cells. Finally, Zhang et al. demonstrated that hsa_circ_0012919 acts as a miRNA sponge for miR-125a-3p, regulating the gene expression of targets RANTES and KLF13 that are involved in the physiology and pathophysiology of acute and chronic inflammatory processes. These findings support the role of circRNAs in the pathophysiology of SLE.

scholarly journals Netosis in the pathogenesis of antiphospholipid syndrome and systemic lupus erythematosus

2021 ◽  
Vol 15 (5) ◽  
pp. 96-102
Author(s):  
K. S. Nurbaeva ◽  
T. M. Reshetnyak ◽  
A. M. Lila
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Space Form ◽  
Clinical Manifestations ◽  
Immunosuppressive Drugs ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Activated Neutrophils

Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are autoimmune diseases. In recent years, APS has been considered as an autoimmune thrombo-inflammatory disease. It has been established that clinical manifestations of APS can persist, progress over time, or debut during an adequate anticoagulant therapy and, in some cases, require administration of immunosuppressive drugs, which indicates the role of autoimmune inflammation in their development. The formation of extracellular neutrophil traps (neutrophil extracellular traps, NETs) is one of the connecting links of inflammation and thrombosis. Netosis is the process by which activated neutrophils in the extracellular space form netlike structures (NETs). This review examines the role of neutrophils and netosis in the pathogenesis of APS and SLE.

scholarly journals Regulation of CD4+CD25+FOXP3+ Treg Cells in Systemic Lupus Erythematosus (SLE): Association With miRNAs Expression

2021 ◽  
Author(s):  
Abeer M. El-Maghraby ◽  
Yasser B.M. Ali ◽  
Eman El-maadawy ◽  
Mohamed F. Elshal ◽  
Iman H Bassyouni ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Treg Cells ◽  
Regulatory Function ◽  
Maximum Increase ◽  
Peripheral Blood Mononuclear ◽  
Diagnostic Role ◽  
Mirnas Expression

Abstract Various genetic factors are controlling regulatory cells T (Treg) cell function, such as miRNAs. Interfering in the miRNA synthesis pathway in Treg cells could result in loss of Tregs' regulatory function, leading to the promotion of inflammatory settings and autoimmunity. This study was designed to investigate the role of miRNA in regulating Treg cells in SLE patients. Treg's frequency was determined using flow cytometry in 100 SLE patients’ and100 healthy controls. Expression of miR-21, miR-24, miR125, miR-146a, miR-148a, and miR-155 was estimated in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction (qRT-PCR). The ROC curve evaluated the diagnostic role of miRNAs in SLE. A significant elevation (p<0.001) in Treg cells in SLE patients than controls was observed, with a maximum increase inactive SLE cases. SLE patients exhibit a significant increase in miR-21 (p<0.01), miR-148a (p<0.001), miR-146a (p<0.05) and miR-155 (p<0.001) and significant reduction in miR-24 (p<0.001). An insignificant decrease in miR-125 was observed in SLE patients. The best sensitivity and specificity were detected in miR-148a (88%, 70%) at a cutoff value of 1. 065. Tregs were positively correlated with miR-21(r=0.333, p<0.05), miR-146a (r=0.589, p<0.01) and miR-148a (r=0.309, p<0.05). In conclusion, this research provides a piece of novel information regarding Treg cells' in SLE patients. Our results pointed to the substantial role of miRNAs in controlling Treg cells in lupus. To validate our interesting results, more researches are needed.

scholarly journals Role of neutrophil dysfunction in the pathogenesis of systemic lupus erythematosus

2017 ◽  
Vol 89 (12) ◽  
pp. 110-113 ◽  
Author(s):  
E V Smirnova ◽  
T N Krasnova ◽  
E V Proskurnina ◽  
N A Mukhin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Protective Function ◽  
Extracellular Traps ◽  
Novel Drugs ◽  
Subsequent Degradation ◽  
Extracellular Environment ◽  
Neutrophil Dysfunction

Neutrophil dysfunction plays a considerable role.in systemic lupus erythematosus (SLE) The protective function of neutrophils is carried out through various mechanisms: isolation of granular antimicrobial peptides (gAMP), microbial phagocytosis with subsequent degradation via reactive oxygen species inside the phagolysosomes; as well as bactericidal action due to the release of networks from chromatin and gAMP, also called neutrophil extracellular traps (NECTs). The development of neutropenia in SLE has multiple causes, including the formation of antibodies directly to leukocytes; that of neutralizing autoantibodies to the growth factors of neutrophils and cells - myeloid precursors; bone marrow suppression; involvement of neutrophils in the processes of apoptosis and NETosis. Neutrophils in SLE are characterized by reduced phagocytic ability and pathological oxidative activity. In SLE, there is a decrease in the ability to remove the products of neutrophil apoptosis, which is correlated with disease activity. SLE patients are noted to have a higher expression level of the genes specific for low-density granulocytes, an abnormal immature neutrophil population. The impaired processes of formation of NECTs and removal NETosis products play a substantial role in the pathogenesis of SLE. It is shown that the abnormal formation of NECTs also causes endothelial injury and increases the risk of thromboses. The design of novel drugs that act on the specific parts of the formation of NECTs or contribute to their removal from the extracellular environment can propel therapy for SLE and other autoimmune diseases to new heights. There is evidence for further investigations of neutrophil-mediated pathogenetic processes in SLE in order to identify potential therapeutic targets and to understand the mechanisms of action of drugs used in clinical practice.

scholarly journals The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis and Complications of Malignant Diseases

2020 ◽  
Author(s):  
Sheniz Yuzeir ◽  
Liana Gercheva
Keyword(s):  
Current Knowledge ◽  
Tumour Progression ◽  
Neutrophil Extracellular Traps ◽  
Malignant Diseases ◽  
Extracellular Traps ◽  
Pathological Conditions ◽  
Inflammatory Processes ◽  
Thrombotic Complications ◽  
Clinically Significant

It was recently proved that neutrophils and platelets are active participants in some inflammatory processes as well as a number of pathological conditions, including neoplastic diseases and thrombosis. It has been found that circulating neutrophils actively affect the mechanisms of tumour genesis, and along with platelets, act as independent regulators of different complications in infectious and malignant diseases. A few years ago, it was found that neutrophils have the ability to release extracellular traps (called neutrophil extracellular traps or NETs). Thus, neutrophils use both intracellular and extracellular mechanisms to limit inflammatory complications. Several recent studies confirmed that NETs increase considerably in malignant diseases, demonstrating that tumour-induced NETosis is a clinically significant process. It is recognised as an element of tumour biology, as it participates in tumour progression and angiogenesis. Neutrophils and the NETs released from them are stimulators of thrombotic processes in physiological and pathological conditions. Several reports demonstrate the connection between NETs and thrombosis. The presence of NETosis serves as a potential risk factor for thrombotic complications in malignant diseases. This chapter summarises the current knowledge of NETosis and the mechanisms that lead to the formation of NETs, including the role of circulating platelet–neutrophil complexes as regulators of tumour-induced NETosis in malignant diseases.

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