Journal of Innate Immunity最新文献_第6页

Basic Mechanisms of Immunometabolites in Shaping the Immune Response. 免疫代谢物在形成免疫反应中的基本机制。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-11-23 DOI: 10.1159/000535452

Dylan Gerard Ryan, Christian Graham Peace, Alexander Hooftman

{"title":"Basic Mechanisms of Immunometabolites in Shaping the Immune Response.","authors":"Dylan Gerard Ryan, Christian Graham Peace, Alexander Hooftman","doi":"10.1159/000535452","DOIUrl":"10.1159/000535452","url":null,"abstract":"Background: Innate immune cells play a crucial role in responding to microbial infections, but their improper activation can also drive inflammatory disease. For this reason, their activation state is governed by a multitude of factors, including the metabolic state of the cell and, more specifically, the individual metabolites which accumulate intracellularly and extracellularly. This relationship is bidirectional, as innate immune cell activation by pathogen-associated molecular patterns causes critical changes in cellular metabolism.Summary: In this review, we describe the emergence of various \"immunometabolites.\" We outline the general characteristics of these immunometabolites, the conditions under which they accumulate, and their subsequent impact on immune cells. We delve into well-studied metabolites of recent years, such as succinate and itaconate, as well as newly emerging immunometabolites, such as methylglyoxal.Key messages: We hope that this review may be used as a framework for further studies dissecting the mechanisms by which immunometabolites regulate the immune system and provide an outlook to harnessing these mechanisms in the treatment of inflammatory diseases.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"925-943"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

C-Terminal PEGylation Improves SAAP-148 Peptide's Immunomodulatory Activities. C-末端PEG化提高SAAP-148肽的免疫调节活性。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-19 DOI: 10.1159/000534068

Miriam E van Gent, Bep Schonkeren-Ravensbergen, Asma Achkif, Daan Beentjes, Natasja Dolezal, Krista E van Meijgaarden, Jan Wouter Drijfhout, Peter H Nibbering

{"title":"C-Terminal PEGylation Improves SAAP-148 Peptide's Immunomodulatory Activities.","authors":"Miriam E van Gent, Bep Schonkeren-Ravensbergen, Asma Achkif, Daan Beentjes, Natasja Dolezal, Krista E van Meijgaarden, Jan Wouter Drijfhout, Peter H Nibbering","doi":"10.1159/000534068","DOIUrl":"10.1159/000534068","url":null,"abstract":"Synthetic antibacterial and anti-biofilm peptide (SAAP)-148 was developed to combat bacterial infections not effectively treatable with current antibiotics. SAAP-148 is highly effective against antimicrobial-resistant bacteria without inducing resistance; however, challenges for further development of SAAP-148 include its cytotoxicity and short circulation half-life. To circumvent these drawbacks, a library of SAAP-148 linked to polyethylene glycol (PEG) groups of various lengths was synthesized and screened for in vitro antibacterial activity and hemolytic activity. Results indicated that PEGylated SAAP-148 variants combine antibacterial activities with reduced hemolysis compared to SAAP-148. Interestingly, proinflammatory immunomodulatory activities of SAAP-148 were enhanced upon C-terminal PEGylation, with SAAP-148-PEG27 showing the most effect. SAAP-148-PEG27 enhanced SAAP-148's capacity to chemoattract human neutrophils and was able to more efficiently (re)direct M-CSF-induced monocyte-macrophage differentiation toward type 1 macrophages as opposed to SAAP-148. Furthermore, dendritic cells with a stronger mature expression profile were produced if monocytes were exposed to SAAP-148-PEG27 during monocyte-immature dendritic cell differentiation in comparison to SAAP-148. Parameters that influenced the immunomodulatory activities of the peptide-PEG conjugate include (i) the length of the PEG group, (ii) the position of PEG conjugation, and (iii) the peptide sequence. Together, these results indicate that SAAP-148-PEG27 is highly effective in redirecting monocyte-macrophage differentiation toward a proinflammatory phenotype and promoting monocyte-mature dendritic cell development. Therefore, SAAP-148-PEG27 may be a promising agent to modulate inadequate immune responses in case of tumors and chronically infected wounds.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"724-738"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/f2/jin-2023-0015-0001-534068.PMC10601628.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Selected β-Glucans Act as Immune-Training Agents by Improving Anti-Mycobacterial Activity in Human Macrophages: A Pilot Study. 一项初步研究表明，选定的β-葡聚糖通过提高人体巨噬细胞的抗分枝杆菌活性，起到免疫训练剂的作用。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-21 DOI: 10.1159/000533873

Clara Braian, Lovisa Karlsson, Jyotirmoy Das, Maria Lerm

{"title":"Selected β-Glucans Act as Immune-Training Agents by Improving Anti-Mycobacterial Activity in Human Macrophages: A Pilot Study.","authors":"Clara Braian, Lovisa Karlsson, Jyotirmoy Das, Maria Lerm","doi":"10.1159/000533873","DOIUrl":"10.1159/000533873","url":null,"abstract":"Epigenetic reprogramming of innate immune cells by β-glucan in a process called trained immunity leads to an enhanced host response to a secondary infection. β-Glucans are structural components of plants, algae, fungi, and bacteria and thus recognized as non-self by human macrophages. We selected the β-glucan curdlan from Alcaligenes faecalis, WGP dispersible from Saccharomyces cerevisiae, and β-glucan-rich culture supernatant of Alternaria and investigated whether they could produce trained immunity effects leading to an increased control of virulent Mycobacterium tuberculosis. We observed a significant M. tuberculosis growth reduction in macrophages trained with curdlan and Alternaria, which also correlated with increased IL-6 and IL-1β release. WGP dispersible-trained macrophages were stratified into \"non-responders\" and \"responders,\" according to their ability to control M. tuberculosis, with \"responders\" producing higher IL-6 levels. The addition of neutrophils to infected macrophage cultures further enhanced macrophage control of virulent M. tuberculosis, but not in a stimuli-dependent manner. Pathway enrichment analysis of DNA methylome data also highlighted hypomethylation of genes in pathways associated with signaling and cellular reorganization and motility, and \"responders\" to WGP training were enriched in the interferon-gamma signaling pathway. This study adds evidence that certain β-glucans show promise as immune-training agents.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"751-764"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41139014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1. MicroRNA-9-1通过靶向Tankyrase 1减弱甲型流感病毒复制。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-08-22 DOI: 10.1159/000532063

Gayan Bamunuarachchi, Kishore Vaddadi, Xiaoyun Yang, Quanjin Dang, Zhengyu Zhu, Sankha Hewawasam, Chaoqun Huang, Yurong Liang, Yujie Guo, Lin Liu

{"title":"MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1.","authors":"Gayan Bamunuarachchi, Kishore Vaddadi, Xiaoyun Yang, Quanjin Dang, Zhengyu Zhu, Sankha Hewawasam, Chaoqun Huang, Yurong Liang, Yujie Guo, Lin Liu","doi":"10.1159/000532063","DOIUrl":"10.1159/000532063","url":null,"abstract":"An unstable influenza genome leads to the virus resistance to antiviral drugs that target viral proteins. Thus, identification of host factors essential for virus replication may pave the way to develop novel antiviral therapies. In this study, we investigated the roles of the poly(ADP-ribose) polymerase enzyme, tankyrase 1 (TNKS1), and the endogenous small noncoding RNA, miR-9-1, in influenza A virus (IAV) infection. Increased expression of TNKS1 was observed in IAV-infected human lung epithelial cells and mouse lungs. TNKS1 knockdown by RNA interference repressed influenza viral replication. A screen using TNKS1 3'-untranslation region (3'-UTR) reporter assays and predicted microRNAs identified that miR-9-1 targeted TNKS1. Overexpression of miR-9-1 reduced influenza viral replication in lung epithelial cells as measured by viral mRNA and protein levels as well as virus production. miR-9-1 induced type I interferon production and enhanced the phosphorylation of STAT1 in cell culture. The ectopic expression of miR-9-1 in the lungs of mice by using an adenoviral viral vector enhanced type I interferon response, inhibited viral replication, and reduced susceptibility to IAV infection. Our results indicate that miR-9-1 is an anti-influenza microRNA that targets TNKS1 and enhances cellular antiviral state.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"647-664"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/85/jin-2023-0015-0001-532063.PMC10601686.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N6-Methyladenosine (m6A) Modification in Natural Immune Cell-Mediated Inflammatory Diseases. 天然免疫细胞介导的炎症性疾病中的N6-甲基腺苷（m6A）修饰。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-10-30 DOI: 10.1159/000534162

Yan Teng, Jin Yi, Junnian Chen, Lu Yang

引用次数: 0

CLIPB4 Is a Central Node in the Protease Network that Regulates Humoral Immunity in Anopheles gambiae Mosquitoes. CLIPB4是调节冈比亚按蚊体液免疫的蛋白酶网络中的一个中心节点。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-09-13 DOI: 10.1159/000533898

Xiufeng Zhang, Shasha Zhang, Junyao Kuang, Kathleen A Sellens, Bianca Morejon, Sally A Saab, Miao Li, Eve C Metto, Chunju An, Christopher T Culbertson, Mike A Osta, Caterina Scoglio, Kristin Michel

{"title":"CLIPB4 Is a Central Node in the Protease Network that Regulates Humoral Immunity in Anopheles gambiae Mosquitoes.","authors":"Xiufeng Zhang, Shasha Zhang, Junyao Kuang, Kathleen A Sellens, Bianca Morejon, Sally A Saab, Miao Li, Eve C Metto, Chunju An, Christopher T Culbertson, Mike A Osta, Caterina Scoglio, Kristin Michel","doi":"10.1159/000533898","DOIUrl":"10.1159/000533898","url":null,"abstract":"Insect humoral immune responses are regulated in part by protease cascades, whose components circulate as zymogens in the hemolymph. In mosquitoes, these cascades consist of clip-domain serine proteases (cSPs) and/or their non-catalytic homologs, which form a complex network, whose molecular make-up is not fully understood. Using a systems biology approach, based on a co-expression network of gene family members that function in melanization and co-immunoprecipitation using the serine protease inhibitor (SRPN)2, a key negative regulator of the melanization response in mosquitoes, we identify the cSP CLIPB4 from the African malaria mosquito Anopheles gambiae as a central node in this protease network. CLIPB4 is tightly co-expressed with SRPN2 and forms protein complexes with SRPN2 in the hemolymph of immune-challenged female mosquitoes. Genetic and biochemical approaches validate our network analysis and show that CLIPB4 is required for melanization and antibacterial immunity, acting as a prophenoloxidase (proPO)-activating protease, which is inhibited by SRPN2. In addition, we provide novel insight into the structural organization of the cSP network in An. gambiae, by demonstrating that CLIPB4 is able to activate proCLIPB8, a cSP upstream of the proPO-activating protease CLIPB9. These data provide the first evidence that, in mosquitoes, cSPs provide branching points in immune protease networks and deliver positive reinforcement in proPO activation cascades.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"680-696"},"PeriodicalIF":4.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/37/jin-2023-0015-0001-533898.PMC10603620.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interleukin-33 Ameliorates Murine Systemic Lupus Erythematosus and Is Associated with Induction of M2 Macrophage Polarisation and Regulatory T Cells. 白细胞介素-33 可改善小鼠系统性红斑狼疮，并与 M2 巨噬细胞极化和调节性 T 细胞的诱导有关。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-03-08 DOI: 10.1159/000529931

Mo Yin Mok, Ka Sin Law, Wing Yin Kong, Cai Yun Luo, Endale T Asfaw, Kwok Wah Chan, Fang Ping Huang, Chak Sing Lau, Godfrey Chi Fung Chan

{"title":"Interleukin-33 Ameliorates Murine Systemic Lupus Erythematosus and Is Associated with Induction of M2 Macrophage Polarisation and Regulatory T Cells.","authors":"Mo Yin Mok, Ka Sin Law, Wing Yin Kong, Cai Yun Luo, Endale T Asfaw, Kwok Wah Chan, Fang Ping Huang, Chak Sing Lau, Godfrey Chi Fung Chan","doi":"10.1159/000529931","DOIUrl":"10.1159/000529931","url":null,"abstract":"The innate cytokine IL-33 is increasingly recognised to possess biological effects on various immune cells. We have previously demonstrated elevated serum level of soluble ST2 in patients with active systemic lupus erythematosus suggesting involvement of IL-33 and its receptor in the lupus pathogenesis. This study sought to examine the effect of exogenous IL-33 on disease activity of pre-disease lupus-prone mice and the underlying cellular mechanisms. Recombinant IL-33 was administered to MRL/lpr mice for 6 weeks, whereas control group received phosphate-buffered saline. IL-33-treated mice displayed less proteinuria, renal histological inflammatory changes, and had lower serum levels of pro-inflammatory cytokines including IL-6 and TNF-α. Renal tissue and splenic CD11b+ extracts showed features of M2 polarisation with elevated mRNA expression of Arg1, FIZZI, and reduced iNOS. These mice also had increased IL-13, ST2, Gata3, and Foxp3 mRNA expression in renal and splenic tissues. Kidneys of these mice displayed less CD11b+ infiltration, had downregulated MCP-1, and increased infiltration of Foxp3-expressing cells. Splenic CD4+ T cells showed increased ST2-expressing CD4+Foxp3+ population and reduced IFN-γ+ population. There were no differences in serum anti-dsDNA antibodies and renal C3 and IgG2a deposit in these mice. Exogenous IL-33 was found to ameliorate disease activity in lupus-prone mice with induction of M2 polarisation, Th2 response, and expansion of regulatory T cells. IL-33 likely orchestrated autoregulation of these cells through upregulation of ST2 expression.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"485-498"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9352307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combined Heterozygous Genetic Variations in Complement C2 and C8B: An Explanation for Multidimensional Immune Imbalance? 补体 C2 和 C8B 的组合杂合遗传变异：多维免疫失衡的解释？

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-03-01 DOI: 10.1159/000528607

Marco Mannes, Rebecca Halbgebauer, Lisa Wohlgemuth, David Alexander Christian Messerer, Susa Savukoski, Anke Schultze, Bettina Berger, Christiane Leonie Knapp, Christoph Q Schmidt, Daniel Fürst, Morten Hillmer, Reiner Siebert, Oskar Eriksson, Barbro Persson, Bo Nilsson, Kristina Nilsson Ekdahl, Markus Huber-Lang

{"title":"Combined Heterozygous Genetic Variations in Complement C2 and C8B: An Explanation for Multidimensional Immune Imbalance?","authors":"Marco Mannes, Rebecca Halbgebauer, Lisa Wohlgemuth, David Alexander Christian Messerer, Susa Savukoski, Anke Schultze, Bettina Berger, Christiane Leonie Knapp, Christoph Q Schmidt, Daniel Fürst, Morten Hillmer, Reiner Siebert, Oskar Eriksson, Barbro Persson, Bo Nilsson, Kristina Nilsson Ekdahl, Markus Huber-Lang","doi":"10.1159/000528607","DOIUrl":"10.1159/000528607","url":null,"abstract":"The complement system plays a crucial role in host defense, homeostasis, and tissue regeneration and bridges the innate and the adaptive immune systems. Although the genetic variants in complement C2 (c.839_849+17del; p.(Met280Asnfs*5)) and C8B (c.1625C>T; p.(Thr542Ile)) are known individually, here, we report on a patient carrying their combination in a heterozygous form. The patient presented with a reduced general condition and suffers from a wide variety of autoimmune diseases. While no autoimmune disease-specific autoantibodies could be detected, genetic analysis revealed abnormalities in the two complement genes C2 and C8B. Therefore, we performed a comprehensive investigation of the innate immune system on a cellular and humoral level to define the functional consequences. We found slightly impaired functionality of neutrophils and monocytes regarding phagocytosis and reactive oxygen species generation and a diminished expression of the C5aR1. An extensive complement analysis revealed a declined activation potential for the alternative and classical pathway. Reconstitution with purified C2 and C8 into patient serum failed to normalize the dysfunction, whereas the addition of C3 improved the hemolytic activity. In clinical transfer, in vitro supplementation of the patient's plasma with FFP as a complement source could fully restore full complement functionality. This study describes for the first time a combined heterozygous genetic variation in complement C2 and C8B which, however, cannot fully explain the overall dysfunctions and calls for further complement deficiency research and corresponding therapies.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"15 1","pages":"412-427"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/d3/jin-2023-0015-0001-528607.PMC10015110.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional Analysis of a Novel Complement C5a Receptor 1-Blocking Monoclonal Antibody. 一种新型补体C5a受体1阻断单克隆抗体的功能分析。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-11-10 DOI: 10.1159/000535084

Leon Cyranka, Ida Mariegaard, Mikkel-Ole Skjødt, Rafael Bayarri-Olmos, Tom Eirik Mollnes, Peter Garred, Anne Rosbjerg

{"title":"Functional Analysis of a Novel Complement C5a Receptor 1-Blocking Monoclonal Antibody.","authors":"Leon Cyranka, Ida Mariegaard, Mikkel-Ole Skjødt, Rafael Bayarri-Olmos, Tom Eirik Mollnes, Peter Garred, Anne Rosbjerg","doi":"10.1159/000535084","DOIUrl":"10.1159/000535084","url":null,"abstract":"Introduction: The complement system anaphylatoxin C5a is a critical player in inflammation. By binding to complement C5a receptor 1 (C5aR1/CD88), C5a regulates many cellular functions, mainly as a potent pro-inflammatory inducer. We describe the generation and selection of a potent antagonistic C5aR1 mouse monoclonal antibody (mAb).Methods: Initial C5aR1 hybridoma clone selection was performed with a cell-binding study in human whole blood. In-house C5aR1 mAb assessment for C5aR1 inhibition was done via the iLite® C5a assay. C5aR1 mAb specificity was investigated on C5aR1his- and C5aR2his-expressing Flp-In™-CHO cells. Physiological C5aR1 inhibition was assessed via a C5a-driven calcium flux assay and stimulation assay based on isolated polymorphonuclear leukocytes (PMNs) and a whole blood model stimulated with Escherichia coli.Results: The supernatant of hybridoma clones targeting the N-terminal section of C5aR1 displayed efficient binding to C5aR1 in whole blood, which was confirmed for purified mAbs. The C5aR1 mAb 18-41-6 was selected following the assay of in-house C5aR1 mAbs via the iLite® C5a assay. The mAb 18-41-6 was specific for C5aR1. Full-size and/or F(ab')2 preparations of mAb 18-41-6 were found to efficiently abrogate C5a-induced calcium flux in neutrophils and to significantly reduce the upregulation of the activation markers CD11b (neutrophils, monocytes) and CD66b (neutrophils).Conclusion: Our results demonstrate that mAb 18-41-6 is a valuable tool for investigating the C5a-C5aR1 axis and a potential therapeutic candidate for inflammatory disease treatment.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"836-849"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10691831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenotypic Characterization of Acoustically Enriched Extracellular Vesicles from Pathogen-Activated Platelets. 病原体激活的血小板中富含声学的细胞外小泡的表型特征。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-05-27 DOI: 10.1159/000531266

Frida Palm, Axel Broman, Genevieve Marcoux, John W Semple, Thomas L Laurell, Johan Malmström, Oonagh Shannon

{"title":"Phenotypic Characterization of Acoustically Enriched Extracellular Vesicles from Pathogen-Activated Platelets.","authors":"Frida Palm, Axel Broman, Genevieve Marcoux, John W Semple, Thomas L Laurell, Johan Malmström, Oonagh Shannon","doi":"10.1159/000531266","DOIUrl":"10.1159/000531266","url":null,"abstract":"Extracellular vesicles (EVs) are derived from the membrane of platelets and released into the circulation upon activation or injury. Analogous to the parent cell, platelet-derived EVs play an important role in hemostasis and immune responses by transfer of bioactive cargo from the parent cells. Platelet activation and release of EVs increase in several pathological inflammatory diseases, such as sepsis. We have previously reported that the M1 protein released from the bacterial pathogen Streptococcus pyogenes directly mediates platelet activation. In this study, EVs were isolated from these pathogen-activated platelets using acoustic trapping, and their inflammation phenotype was characterized using quantitative mass spectrometry-based proteomics and cell-based models of inflammation. We determined that M1 protein mediated release of platelet-derived EVs that contained the M1 protein. The isolated EVs derived from pathogen-activated platelets contained a similar protein cargo to those from physiologically activated platelets (thrombin) and included platelet membrane proteins, granule proteins, cytoskeletal proteins, coagulation factors, and immune mediators. Immunomodulatory cargo, complement proteins, and IgG3 were significantly enriched in EVs isolated from M1 protein-stimulated platelets. Acoustically enriched EVs were functionally intact and exhibited pro-inflammatory effects on addition to blood, including platelet-neutrophil complex formation, neutrophil activation, and cytokine release. Collectively, our findings reveal novel aspects of pathogen-mediated platelet activation during invasive streptococcal infection.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"599-613"},"PeriodicalIF":5.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9532783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0