B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH最新文献

{"title":"Differential Responses to Inhibition of Glutamine Metabolism Between Alveolar and Bone Marrow-Derived Macrophages","authors":"C. L. Vigeland, R.T. Moore, H. S. Beggs, H. Dang, C. Doerschuk","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2616","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2616","url":null,"abstract":"","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"103 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115113659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dual-Endothelin1/VEGFsp Receptor (DEspR) - Potential Role in Chronic Respiratory Diseases","authors":"S. Carstensen, J. Hohlfeld, N. Ruiz‐Opazo, V. Herrera, M. Müller","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2621","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2621","url":null,"abstract":"Background The translatability of the dual-endothelin1/VEGFsp receptor (DEspR) in human was first described in 2016 and its functionality is largely unknown since DEspR is not expressed in healthy human tissues except for kidney tissue and certain tumors. Recently, DEspR expression was reported on human neutrophil subsets of acute respiratory distress syndrome (ARDS) and COVID19-ADRS patients. DEspR+ neutrophil levels correlated with disease severity and mortality which may root in their delayed apoptosis and facilitated formation of neutrophil extracellular traps. Neutrophils play a major role in inflammation of chronic respiratory diseases and altered levels of DEspR ligands ET-1 and VEGF are found in COPD and asthma phenotypes. Here, we investigated the DEspR expression on human leukocyte populations of asthmatics, COPD patients and healthy smokers as well as on the human promyelocytic leucaemic cell line HL-60. Methods DEspR expression was measured on undifferentiated, promyelocytic HL-60 cells and after differentiation towards a neutrophilic phenotype using 1.25% DMSO. Expression was also measured after stimulation with 50 μg/mL poly I:C or 100 ng/mL LPS. Whole blood cells of COPD patients (step III, IV), healthy smokers and asthmatics (step III) were stained directly after blood draw or after stimulation with 50 μg/mL poly I:C or 100 ng/mL LPS. HL-60 and whole blood leukocytes were stained with Annexin V, 7AAD, DEspR (rhIgG4, clone 6g8), CD11b, CD14 and CD16a. Results Undifferentiated CD11b-, CD14- CD16a- and differentiated CD11b+, CD14-, CD16a- HL-60 cells did not express DEspR, neither with or without inflammatory stimulation. DespR was not expressed on whole blood leukocytes at baseline level (mean±SD: 0.15±0.26 to 0.91±0.60%) but poly I:C induced DEspR expression on neutrophils (34.10±18.52%), monocytes (29.16±20.00%), lymphocytes (9.67±6.11%) and eosinophils (6.14±4.39%). The distribution of DEspR+ cells upon poly I:C stimulation was not significantly altered among different disease types, however, healthy smokers showed a trend to higher DEspR levels. The median fluorescence intensity was not significantly altered among disease types but among the cell populations. Conclusion First experiments demonstrated that DEspR expression can be induced on leukocytes upon inflammatory stimulation. In contrast to previous results of us, LPS did not induce DEspR expression which might be related to differences in the age and disease severity of investigated patients. Interestingly, poly I:C induced a strong DEspR expression indicating a toll-like receptor 3 related mechanism. The sample size needs to be increased to confirm these first results and to investigate the underlying mechanism in detail.","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125320647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of the Structural Requirements for the Immunomodulatory Surfactant Protein D (SP-D) to Bind to Maltose Based Ligands","authors":"J. Madsen, Y. Ghrabigi, T. C. Hernandez, T. Greenhough, A. Shrive, H. Clark, Elizabeth, Garrett Anderson","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2609","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2609","url":null,"abstract":"Introduction: Surfactant protein D (SP-D) is an important part of the airway innate immune system, responsible for clearance of invading pathogens. As a calcium dependent collagenous lectin, SP-D belongs to the collectin family and uses its carbohydrate recognition domain to interact with ligands on microbes such as bacteria and viruses. An understanding of how the lectin domain of human SP-D interacts with selected saccharides","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"111 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129049711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Innate Host Response to Influenza Virus in Brains of Aged Mice","authors":"W. Wu, S.E. Feher, B. Cassidy, W. Zhang, L. Tian, D. Drevets, J. Metcalf","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2602","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2602","url":null,"abstract":"","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"100 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124777980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous Immunoglobulin but Not Dexamethasone Inhibits Neutrophil Pro-Inflammatory Activity While Maintaining Key Antimicrobial Functions","authors":"J.A. Masso Silva, G. Sakoulas, J. Olay, V. Groysberg, V. Nizet, L. C. Crotty Alexander, A. Meier","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2590","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2590","url":null,"abstract":"Rationale. Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical disease. ARDS immunopathology due to lung infection involves an array of immune cells and the importance of granulocytes, and in particular neutrophils and neutrophil extracellular trap production (NETosis), has recently come to light. Despite over 20 well run, randomized, controlled trials, no specific therapies for ARDS are available and mortality remains high. Current treatments for ARDS are primarily limited to supportive therapies, including lung protective ventilation, and in certain situations, systemic steroid administration. Recently, clinical studies adding intravenous immunoglobulin (IVIG), an FDA approved drug, to standard ARDS therapy have shown faster recovery with less severe symptoms, suggesting a complementary beneficial effect, but the mechanism(s) remain unknown. Interestingly, previous in vitro studies found that IVIG can impair some inflammatory pathways in neutrophils. Our study assessed effects of IVIG with and without dexamethasone (a key glucocorticoid used in COVID-19 ARDS) in neutrophils ex vivo and in vivo in COVID-19 patients. Methods. Ex vivo treatment of neutrophils with IVIG or dexamethasone was conducted, followed by assessment of NETosis, oxidative burst and phagocytosis. Additionally, cell-free DNA was quantified in the blood of COVID-19 patients before and after treatment with IVIG. Ex vivo NETosis and plasma cell-free DNA was quantified using the QuantiT ™ PicoGreen™ dsDNA Assay Kit (Invitrogen). Oxidative burst was assessed by OxyBURST™ Green H2DCFDA, SE (Invitrogen) and phagocytosis of pHrodo™ Red S. aureus Bioparticles™ (Invitrogen) was quantified. Results. IVIG inhibits crucial neutrophil inflammatory pathways such as NETosis and oxidative burst while concomitantly enhancing phagocytic activity (Figure panels A-C). Notably, dexamethasone does not impact any of these critical pathways. Moreover, COVID-19 patients undergoing standard treatment plus IVIG had decreased cell-free DNA in the circulation 5 days after initiation of a 4 day treatment course, suggesting decreased NETs in circulation (Figure panel D) which possibly reverted at a later timepoint. Conclusion. Our data demonstrate potential targeted beneficial effects of IVIG in the context of neutrophil-mediated immunopathology. We demonstrate an ex vivo inhibitory effect of IVIG on pro-inflammatory pathways in neutrophils, which may lead to diminished immunopathology in disease states worsened by neutrophil-driven destruction. Based on the compelling evidence of the contribution of neutrophils to development and severity in ARDS, our evidence of IVIG impairing key pro-inflammatory functions in neutrophils (where dexamethasone does not) suggests a theoretical potential complementary beneficial effect of adding IVIG to standard treatment for infection induced ARDS although further research is needed.","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"PP 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126449319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Alterations in the Pulmonary Immune System from Cases of Fatal COVID-19 versus Recovered and Non-Infected Controls","authors":"R. Misra, J. Java, G. Bandyopadhyay, S. Bhattacharya, C. Poole, H. Huyck, G. Deutsch, T. Mariani, G. Pryhuber","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2620","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2620","url":null,"abstract":"","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"252 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122936908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Anti-Inflammatory, Pro-Fibrotic Role of Osteopontin in Influenza A Infection","authors":"M. P. Carbajal, Z. Mark, A. Kumar, N. Daphtary, M. Aliyeva, A. Jegga, J. Bates, V. Anathy","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2619","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2619","url":null,"abstract":"","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"222 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132352015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Thrombosis Promotes Sever Flu in Mice Exposed to Cigarette Smoke","authors":"T.W. Kaminski, T. Brzóska, K. Robinson, T. Nyunoya, P. Sundd","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2597","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2597","url":null,"abstract":"","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"38 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122226440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Tolerability of the Toll-Like Receptor (TLR)2/6 Agonist INNA-051 in Healthy Adults","authors":"S. White, C. Lemech, R. Hari, N. Kruger, G. McLachlan, C. Demaison, F. Mercuri","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2598","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2598","url":null,"abstract":"RATIONALE: INNA-051 is a Toll-like receptor (TLR) 2/6 agonist delivered via intranasal spray, being developed for treatment of respiratory viral diseases. Pre-clinical studies demonstrate that INNA-051 and analogues are effective against a variety of respiratory viruses including SARS-CoV- 2, influenza, and rhinovirus. INNA-051 induces a tissue-localized innate immune response with cytokine expression and infiltration of innate immune cells into the nasal epithelium that play a key role in viral clearance. The primary objective of this study (ACTRN12621000607875p) was evaluation of safety and tolerability in healthy adults. METHODS: This was a randomized, doubleblind, placebo-controlled, Phase 1 study of single and multiple ascending INNA-051 intranasal doses, with the total dose split evenly across both nostrils. Sixty-four participants ages 18-55 were enrolled, with 5 cohorts (6 active:2 placebo/cohort) receiving single doses of 20μg, 60μg, 150μg, 300μg, or 600μg, and 3 cohorts (6 active:2 placebo/cohort) receiving 4 total doses of 60μg, 150μg, and 300μg administered every third day. Assessments included adverse events, clinical laboratories, peak inspiratory nasal flow (PINF), and peak expiratory flow (PEF).RESULTS: Sixtyfour participants (36 males:28 females) ages 19-55 years were enrolled. Preliminary blinded results demonstrate that INNA-051 was well tolerated across all single and multiple dose cohorts. Adverse events were predominantly mild, limited to the nasopharynx, and resolved within 24-48 hours. Across single dose cohorts, the most frequent events were nasal congestion/blockage (n=20), nasal erythema/inflammation (n=19), rhinorrhea (n=13) and headache (n=11). Except for the 20-μg cohort with only 2 reports of rhinorrhea, all other single dose cohorts had a similar incidence of the other adverse events with no obvious dose relationship. Across all 3 multiple dose cohorts, nasal erythema/inflammation (n=42) was most frequently reported, followed by nasal congestion/blockage (n=26), rhinorrhea (n=9), and headache (n=9), with no dose-dependent relationship. No participants withdrew from the study due to adverse events. There were no clinically significant changes in clinical chemistry and hematology laboratories across all single and multiple dose cohorts. No consistent decrease in post-dose PNIF assessments were observed, and there were no changes in PEF assessments to suggest lower respiratory tract airway response to intranasal INNA- 051.CONCLUSIONS: Intranasal INNA-051 was well tolerated up to single doses of 600μg and multiple doses of 300μg. Mild, self-limited nasal adverse events as described are possible indicators of tissue-localized innate immune response by INNA-051. Investigation of cytokine levels and gene expression of the intranasal epithelium are needed to specifically determine TLR2/6 engagement by INNA-051.","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116941279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxidasin Deficiency and Exaggerated Inflammatory Response in the Lung","authors":"G. Cheng, Z. Cao, G. Liu, W. Swords","doi":"10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2622","DOIUrl":"https://doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2622","url":null,"abstract":"","PeriodicalId":126856,"journal":{"name":"B31. IMMUNE CELLS AND INFLAMMATORY PATHWAYS DRIVING LUNG INJURY AND INFECTION - VIEWS FROM THE BENCH","volume":"76 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114445651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}