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10.3389/fimmu.2022.834988 http://scihub22266oqcxt.onion/10.3389/fimmu.2022.834988 35309299!8928747!35309299     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Front+Immunol 2022 ; 13 (ä): 834988 Nephropedia Template TP {{tp|p=35309299|t=2022. Signaling Through FcgammaRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19 |pdf=|usr=}}{{35309299}} gab.com Text Signaling Through FcgammaRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19 JO: Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=35309299 #FOAvip Patients with COVID-19 present with a wide variety of clinical manifestations. Thromboembolic events constitute a significant cause of morbidity and mortality in patients infected with SARS-CoV-2. Severe COVID-19 has been associated with hyperinflammation and pre-existing cardiovascular disease. Platelets are important mediators and sensors of inflammation and are directly affected by cardiovascular stressors. In this report, we found that platelets from severely ill, hospitalized COVID-19 patients exhibited higher basal levels of activation measured by P-selectin surface expression and had poor functional reserve upon in vitro stimulation. To investigate this question in more detail, we developed an assay to assess the capacity of plasma from COVID-19 patients to activate platelets from healthy donors. Platelet activation was a common feature of plasma from COVID-19 patients and correlated with key measures of clinical outcome including kidney and liver injury, and APACHEIII scores. Further, we identified ferritin as a pivotal clinical marker associated with platelet hyperactivation. The COVID-19 plasma-mediated effect on control platelets was highest for patients that subsequently developed inpatient thrombotic events. Proteomic analysis of plasma from COVID-19 patients identified key mediators of inflammation and cardiovascular disease that positively correlated with in vitro platelet activation. Mechanistically, blocking the signaling of the FcgammaRIIa-Syk and C5a-C5aR pathways on platelets, using antibody-mediated neutralization, IgG depletion or the Syk inhibitor fostamatinib, reversed this hyperactivity driven by COVID-19 plasma and prevented platelet aggregation in endothelial microfluidic chamber conditions. These data identified these potentially actionable pathways as central for platelet activation and/or vascular complications and clinical outcomes in COVID-19 patients. In conclusion, we reveal a key role of platelet-mediated immunothrombosis in COVID-19 and identify distinct, clinically relevant, targetable signaling pathways that mediate this effect. Twit Text FOAVip Signaling Through FcgammaRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19 ????Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=35309299 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=35309299 #FOAvip English Wikipedia <ref>{{Cite pmid|35309299}}</ref> Signaling Through FcgammaRIIA and the C5a-C5aR Pathway Mediate Platelet Hyperactivation in COVID-19 #MMPMID35309299 Apostolidis SA; Sarkar A; Giannini HM; Goel RR; Mathew D; Suzuki A; Baxter AE; Greenplate AR; Alanio C; Abdel-Hakeem M; Oldridge DA; Giles JR; Wu JE; Chen Z; Huang YJ; Belman J; Pattekar A; Manne S; Kuthuru O; Dougherty J; Weiderhold B; Weisman AR; Ittner CAG; Gouma S; Dunbar D; Frank I; Huang AC; Vella LA; Reilly JP; Hensley SE; Rauova L; Zhao L; Meyer NJ; Poncz M; Abrams CS; Wherry EJ Front Immunol 2022[]; 13 (ä): 834988 PMID35309299show ga Patients with COVID-19 present with a wide variety of clinical manifestations. Thromboembolic events constitute a significant cause of morbidity and mortality in patients infected with SARS-CoV-2. Severe COVID-19 has been associated with hyperinflammation and pre-existing cardiovascular disease. Platelets are important mediators and sensors of inflammation and are directly affected by cardiovascular stressors. In this report, we found that platelets from severely ill, hospitalized COVID-19 patients exhibited higher basal levels of activation measured by P-selectin surface expression and had poor functional reserve upon in vitro stimulation. To investigate this question in more detail, we developed an assay to assess the capacity of plasma from COVID-19 patients to activate platelets from healthy donors. Platelet activation was a common feature of plasma from COVID-19 patients and correlated with key measures of clinical outcome including kidney and liver injury, and APACHEIII scores. Further, we identified ferritin as a pivotal clinical marker associated with platelet hyperactivation. The COVID-19 plasma-mediated effect on control platelets was highest for patients that subsequently developed inpatient thrombotic events. Proteomic analysis of plasma from COVID-19 patients identified key mediators of inflammation and cardiovascular disease that positively correlated with in vitro platelet activation. Mechanistically, blocking the signaling of the FcgammaRIIa-Syk and C5a-C5aR pathways on platelets, using antibody-mediated neutralization, IgG depletion or the Syk inhibitor fostamatinib, reversed this hyperactivity driven by COVID-19 plasma and prevented platelet aggregation in endothelial microfluidic chamber conditions. These data identified these potentially actionable pathways as central for platelet activation and/or vascular complications and clinical outcomes in COVID-19 patients. In conclusion, we reveal a key role of platelet-mediated immunothrombosis in COVID-19 and identify distinct, clinically relevant, targetable signaling pathways that mediate this effect. |Adult[MESH] |Aminopyridines/pharmacology[MESH] |Blood Platelets/*immunology[MESH] |COVID-19/*immunology[MESH] |Cells, Cultured[MESH] |Complement C5a/*metabolism[MESH] |Female[MESH] |Hospitalization[MESH] |Humans[MESH] |Male[MESH] |Morpholines/pharmacology[MESH] |Platelet Activation[MESH] |Pyrimidines/pharmacology[MESH] |Receptor, Anaphylatoxin C5a/*metabolism[MESH] |Receptors, IgG/*metabolism[MESH] |SARS-CoV-2/*physiology[MESH] |Severity of Illness Index[MESH] |Signal Transduction[MESH] |Syk Kinase/antagonists & inhibitors[MESH]Signaling Through FcgammaRIIA and the C5a-C5aR Pathway Mediate Platele(epmc).pdf DeepDyve Pubget Overpricing