keyword
https://read.qxmd.com/read/38539241/escalated-complement-activation-during-hospitalization-is-associated-with-higher-risk-of-60-day-mortality-in-sars-cov-2-infected-patients
#1
JOURNAL ARTICLE
Andreas Barratt-Due, Kristin Pettersen, Tuva Børresdatter-Dahl, Jan Cato Holter, Renathe H Grønli, Anne Ma Dyrhol-Riise, Tøri Vigeland Lerum, Aleksander Rygh Holten, Kristian Tonby, Marius Trøseid, Ole H Skjønsberg, Beathe Kiland Granerud, Lars Heggelund, Anders Benjamin Kildal, Camilla Schjalm, Trond Mogens Aaløkken, Pål Aukrust, Thor Ueland, Tom Eirik Mollnes, Bente Halvorsen
BACKGROUND: The complement system, an upstream recognition system of innate immunity, is activated upon SARS-CoV-2 infection. To gain a deeper understanding of the extent and duration of this activation, we investigated complement activation profiles during the acute phase of COVID-19, its persistence post-recovery and dynamic changes in relation to disease severity. METHODS: Serial blood samples were obtained from two cohorts of hospitalized COVID-19 patients (n = 457)...
March 27, 2024: Journal of Internal Medicine
https://read.qxmd.com/read/38528025/investigation-of-the-rhythmic-recruitment-of-tear-neutrophils-to-the-ocular-surface-and-their-phenotypes
#2
JOURNAL ARTICLE
Yutong Jin, Ceili Minten, Mara Jenkins, Lyndon Jones, Maud Gorbet
Hundreds of thousands of polymorphonuclear neutrophils (PMNs) are collected from the ocular surface upon waking, while few are harvested during daytime. This study aimed to investigate potential factors contributing to the circadian infiltration of tear PMNs, including changes in IL-8 and C5a in tears, and their phenotypes across different time points in a 24-h cycle. Tear PMNs were collected using a gentle eyewash after 2-h and 7-h of sleep (eye closure, EC) at night, after 2-h EC during the day, and towards the end of the afternoon...
March 25, 2024: Scientific Reports
https://read.qxmd.com/read/38510967/factor-h-related-protein-1-promotes-complement-mediated-opsonization-of-pseudomonas-aeruginosa
#3
JOURNAL ARTICLE
Alex González-Alsina, Héctor Martín-Merinero, Margalida Mateu-Borrás, María Verd, Antonio Doménech-Sánchez, Joanna B Goldberg, Santiago Rodríguez de Córdoba, Sebastián Albertí
Pseudomonas aeruginosa is an important human opportunistic pathogen responsible for a wide range of infections. The complement system is the main early host defense mechanism to control these infections. P. aeruginosa counteracts complement attack by binding Factor H (FH), a complement regulator that inactivates C3b, preventing the formation of the C3-convertase and complement amplification on the bacterial surface. Factor H-related proteins (FHRs) are a group of plasma proteins evolutionarily related to FH that have been postulated to interfere in this bacterial mechanism of resisting complement...
2024: Frontiers in Cellular and Infection Microbiology
https://read.qxmd.com/read/38507201/protein-protein-binding-kinetics-by-biolayer-interferometry
#4
JOURNAL ARTICLE
Jorge Santos-López, Sara Gómez, Francisco J Fernández, M Cristina Vega
The specific kinetics and thermodynamics of protein-protein interactions underlie the molecular mechanisms of cellular functions; hence the characterization of these interaction parameters is central to the quantitative understanding of physiological and pathological processes. Many methods have been developed to study protein-protein interactions, which differ in various features including the interaction detection principle, the sensitivity, whether the method operates in vivo, in vitro, or in silico, the temperature control, the use of labels, immobilization, the amount of sample required, the number of measurements that can be accomplished simultaneously, or the cost...
2024: Advances in Experimental Medicine and Biology
https://read.qxmd.com/read/38505530/staphylococcus-aureus-panton-valentine-leukocidin-worsens-acute-implant-associated-osteomyelitis-in-humanized-brgsf-mice
#5
JOURNAL ARTICLE
Marloes I Hofstee, Claudia Siverino, Motoo Saito, Himanshu Meghwani, James Tapia-Dean, Samson Arveladze, Maria Hildebrand, Javier Rangel-Moreno, Martijn Riool, Stephan Zeiter, Sebastian A J Zaat, T Fintan Moriarty, Gowrishankar Muthukrishnan
Staphylococcus aureus is the most common pathogen that causes implant-associated osteomyelitis, a clinically incurable disease. Immune evasion of S. aureus relies on various mechanisms to survive within the bone niche, including the secretion of leukotoxins such as Panton-Valentine leukocidin (PVL). PVL is a pore-forming toxin exhibiting selective human tropism for C5a receptors (C5aR1 and C5aR2) and CD45 on neutrophils, monocytes, and macrophages. PVL is an important virulence determinant in lung, skin and soft tissue infections...
February 2024: JBMR Plus
https://read.qxmd.com/read/38482828/discovery-and-characterization-of-a-new-class-of-c5ar1-antagonists-showing-in-vivo-activity
#6
JOURNAL ARTICLE
Francis Hubler, Dorte Renneberg, Hervé Siendt, Simon Stamm, Kurt Hilpert, Eva Caroff, Stephane Delahaye, Sylvie Froidevaux, Mark J Murphy
C5a is an anaphylatoxin protein produced by the cleavage of the complement system's component C5 protein. It signals through the G-protein-coupled receptor C5a receptor 1 (C5aR1) to induce the chemotaxis of primarily neutrophils and monocytes and the release of inflammatory molecules. A large body of evidence linking C5aR1 signaling to acute and chronic inflammatory disorders has triggered interest in developing potent C5aR antagonists. Herein we report the discovery of new C5aR1 antagonistic chemical classes...
March 14, 2024: Journal of Medicinal Chemistry
https://read.qxmd.com/read/38482455/a-prospective-observational-study-correlating-possible-novel-biomarkers-with-disease-severity-and-antihistamine-response-in-chronic-spontaneous-urticaria
#7
JOURNAL ARTICLE
Divya Bhatia, Hitaishi Mehta, Anuradha Bishnoi, Niharika Srivastava, Keshavamurthy Vinay, Davinder Parsad, Muthu Sendhil Kumaran
BACKGROUND: Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive. OBJECTIVE: To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients. METHODS: This was a prospective observational study of 95 patients and 42 controls...
March 2024: Asia Pacific Allergy
https://read.qxmd.com/read/38481495/a-prospective-study-on-complement-activation-distinguishes-focal-segmental-glomerulosclerosis-from-minimal-change-disease
#8
JOURNAL ARTICLE
Alexandra Cambier, Natacha Patey, Virginie Royal, François Gougeon, Dominique S Genest, Soumeya Brachemi, Guillaume Bollée, Clémence Merlen, Arnaud Bonnefoy, Anne-Laure Lapeyraque, Stéphan Troyanov
INTRODUCTION: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are related podocytopathies with distinct kidney outcomes. Surprisingly, elevated urinary activation fragments have been found in FSGS despite little complement deposition on immunofluorescence (IF) staining. Whether complement activation distinguishes FSGS from MCD, participating in the development of segmental lesions, remains unknown. METHODS: We performed an observational study in patients with MCD and FSGS, and proteinuria ≥1 g/g of creatinine...
March 2024: KI Reports
https://read.qxmd.com/read/38479702/bacterial-load-in-cerebrospinal-fluid-predicts-unfavourable-outcome-in-pneumococcal-meningitis-a-prospective-nationwide-cohort-study
#9
JOURNAL ARTICLE
Nora Chekrouni, Thijs M van Soest, Ana C da Cruz Campos, Matthijs C Brouwer, Diederik van de Beek
OBJECTIVES: The objective of this study was to determine the role of cerebrospinal fluid (CSF) bacterial load in adults with pneumococcal meningitis. METHODS: We quantified bacterial load in CSF samples from the diagnostic lumbar puncture of adults with community-acquired pneumococcal meningitis. We also measured CSF concentrations of complement 5a (C5a), and determined associations between bacterial load, clinical characteristics, C5a and unfavourable outcome (Glasgow Outcome Scale score<5)...
March 11, 2024: Clinical Microbiology and Infection
https://read.qxmd.com/read/38467968/mitochondrial-damage-and-clearance-in-retinal-pigment-epithelial-cells
#10
JOURNAL ARTICLE
Iswariyaraja Sridevi Gurubaran
Age-related macular degeneration (AMD) is a devastating eye disease that causes permanent vision loss in the central part of the retina, known as the macula. Patients with such severe visual loss face a reduced quality of life and are at a 1.5 times greater risk of death compared to the general population. Currently, there is no cure for or effective treatment for dry AMD. There are several mechanisms thought to underlie the disease, for example, ageing-associated chronic oxidative stress, mitochondrial damage, harmful protein aggregation and inflammation...
March 2024: Acta Ophthalmologica
https://read.qxmd.com/read/38467082/icariin-ameliorates-lps-induced-acute-lung-injury-in-mice-via-complement-c5a-c5ar1-and-tlr4-signaling-pathways
#11
JOURNAL ARTICLE
Jing Guo, Qi-Yun Zhang, Lin Xu, Min Li, Qian-Yun Sun
Acute lung injury (ALI) is an acute respiratory-related progressive disorder, which lacks specific pharmacotherapy. Icariin (ICA) has been shown to be effective in treating ALI. However, the targets and pharmacological mechanisms underlying the effects of ICA in the treatment of ALI are relatively lacking. Based on network pharmacology and molecular docking analyses, the gene functions and potential target pathways of ICA in the treatment of ALI were determined. In addition, the underlying mechanisms of ICA were verified by immunohistochemistry, immunofluorescence, quantitative Real-time PCR, and Western blot in LPS-induced ALI mice...
March 9, 2024: International Immunopharmacology
https://read.qxmd.com/read/38458648/c5ar-plus-mek-inhibition-durably-targets-the-tumor-milieu-and-reveals-tumor-cell-phagocytosis
#12
JOURNAL ARTICLE
Melissa R Perrino, Niousha Ahmari, Ashley Hall, Mark Jackson, Youjin Na, Jay Pundavela, Sara Szabo, Trent M Woodruff, Eva Dombi, Mi-Ok Kim, Jörg Köhl, Jianqiang Wu, Nancy Ratner
Plexiform neurofibromas (PNFs) are nerve tumors caused by loss of NF1 and dysregulation of RAS-MAPK signaling in Schwann cells. Most PNFs shrink in response to MEK inhibition, but targets with increased and durable effects are needed. We identified the anaphylatoxin C5a as increased in PNFs and expressed largely by PNF m acrophages. We defined pharmacokinetic and immunomodulatory properties of a C5aR1/2 antagonist and tested if peptide antagonists augment the effects of MEK inhibition. MEK inhibition recruited C5AR1 to the macrophage surface; short-term inhibition of C5aR elevated macrophage apoptosis and Schwann cell death, without affecting MEK-induced tumor shrinkage...
May 2024: Life Science Alliance
https://read.qxmd.com/read/38452744/the-complement-c3a-and-c5a-signaling-in-renal-diseases-a-bridge-between-acute-and-chronic-inflammation
#13
REVIEW
Simona Buelli, Barbara Imberti, Marina Morigi
The complement system, a cornerstone of the innate immune defense, typically confers protection against pathogens. However, in various clinical scenarios the complement's defensive actions can harm host cells, exacerbating immune and inflammatory responses. The central components C3 and C5 undergo proteolytic cleavage during complement activation, yielding small active fragments C3a and C5a anaphylatoxins. Traditionally these fragments were associated with inflammation via the specific receptors C3a receptor (R), C5aR1 and C5aR2...
March 7, 2024: Nephron
https://read.qxmd.com/read/38449312/c5a-c5ar1-axis-controls-mitochondrial-fission-to-promote-podocyte-injury-in-lupus-nephritis
#14
JOURNAL ARTICLE
Baokui Ye, Binfeng Chen, Chaohuan Guo, Ningjing Xiong, Yuefang Huang, Mengyuan Li, Yimei Lai, Jin Li, Mianjing Zhou, Shuang Wang, Shuyi Wang, Niansheng Yang, Hui Zhang
Podocytes are essential to maintaining the integrity of the glomerular filtration barrier, yet they are frequently affected in lupus nephritis (LN). Here, we show that the significant upregulation of Drp1S616 phosphorylation in podocytes promotes mitochondrial fission, leading to mitochondrial dysfunction and podocyte injury in LN. Inhibition or knockdown of Drp1 promotes mitochondrial fusion and protects podocytes from injury induced by LN serum. In vivo, pharmacological inhibition of Drp1 reduces the phosphorylation of Drp1S616 in podocytes in lupus-prone mice...
March 6, 2024: Molecular Therapy
https://read.qxmd.com/read/38447809/active-immunotherapy-for-c5a-mediated-inflammation-using-adjuvant-free-self-assembled-peptide-nanofibers
#15
JOURNAL ARTICLE
Kelly M Hainline, Helena Freire Haddad, Anna Gilpin, Elizabeth J Curvino, Shyni Varghese, Joel H Collier
The terminal protein in the complement cascade C5a is a potent inflammatory molecule and chemoattractant that is involved in the pathology of multiple inflammatory diseases including sepsis and arthritis, making it a promising protein to target with immunotherapies. Active immunotherapies, in which patients are immunized against problematic self-molecules and generate therapeutic antibodies as a result, have received increasing interest as an alternative to traditional monoclonal antibody treatments. In previous work, we have designed supramolecular self-assembling peptide nanofibers as active immunotherapies with defined combinations of B- and T-cell epitopes...
March 4, 2024: Acta Biomaterialia
https://read.qxmd.com/read/38441324/revisiting-the-relationship-between-complement-and-ulcerative-colitis
#16
REVIEW
Yujie Ma, Kaicheng Zhang, Yuanyuan Wu, Xiaoyan Fu, Shujuan Liang, Meiyu Peng, Juntang Guo, Meifang Liu
Ulcerative colitis (UC) is an inflammatory bowel disorder (IBD) characterized by relapsing chronic inflammation of the colon that causes continuous mucosal inflammation. The global incidence of UC is steadily increasing. Immune mechanisms are involved in the pathogenesis of UC, of which complement is shown to play a critical role by inducing local chronic inflammatory responses that promote tissue damage. However, the function of various complement components in the development of UC is complex and even paradoxical...
November 2023: Scandinavian Journal of Immunology
https://read.qxmd.com/read/38433474/the-complement-system-a-potential-target-for-the-comorbidity-of-chronic-pain-and-depression
#17
REVIEW
Shanshan Tang, Wen Hu, Helin Zou, Qingyang Luo, Wenwen Deng, Song Cao
The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions...
March 4, 2024: Korean Journal of Pain
https://read.qxmd.com/read/38401574/the-complement-system-and-diabetic-retinopathy
#18
REVIEW
Feipeng Jiang, Chunyan Lei, Yingying Chen, Nenghua Zhou, Meixia Zhang
Diabetic retinopathy (DR) is one of the common microvascular complications of diabetes mellitus and is the main cause of visual impairment in diabetic patients. The pathogenesis of DR is still unclear. The complement system, as an important component of the innate immune system, in addition to defending against the invasion of foreign microorganisms, is involved in the occurrence and development of DR through 3 widely recognized complement activation pathways, the complement regulatory system, and many other pathways...
February 22, 2024: Survey of Ophthalmology
https://read.qxmd.com/read/38387717/inhibition-of-colon-c5a-c5a-receptor-signalling-pathway-confers-protection-against-lps-induced-acute-kidney-injury-via-gut-microbiota-kidney-axis
#19
JOURNAL ARTICLE
Rong-Cheng Xie, Jin-Cheng Zhang, Xiao-Ming Lin, Ting Huang, Yu-Ting Wang, Lian-Fang Zhang, Xiang-Yu Hong, Xue-Feng Lin, Hong-Jun Zheng, Zhe Luo, Li-Tao Yi, Jie-Fei Ma
Acute kidney injury (AKI) is a critical condition often associated with systemic inflammation and dysregulated gut microbiota. This study aimed to investigate the effects of the C5a receptor antagonist W54011 on lipopolysaccharide (LPS)-induced AKI, focusing on the colon's C5a/C5a receptor pathway, intestinal barrier integrity, and gut microbiota. Our findings demonstrate that W54011 effectively ameliorated kidney injury in the LPS-induced AKI model by selectively inhibiting the colon's C5a/C5a receptor signalling pathway...
February 20, 2024: European Journal of Pharmacology
https://read.qxmd.com/read/38372645/critical-role-of-cd55-in-controlling-wound-healing
#20
JOURNAL ARTICLE
Lorna Kang, Maryo Kohen, Isaac McCarthy, Emma Hammelef, Hae Suk Kim, R Bapputty, Rose Gubitosi-Klug, Faruk H Orge, Timothy Kern, M Edward Medof
How reparative processes are coordinated following injury is incompletely understood. In recent studies, we showed that autocrine C3a and C5a receptor (C3ar1 and C5ar1) G protein-coupled receptor signaling plays an obligate role in vascular endothelial growth factor receptor 2 growth signaling in vascular endothelial cells. We documented the same interconnection for platelet-derived growth factor receptor growth signaling in smooth muscle cells, epidermal growth factor receptor growth signaling in epidermal cells, and fibroblast growth factor receptor signaling in fibroblasts, indicative of a generalized cell growth regulatory mechanism...
February 19, 2024: Journal of Immunology
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