Document text
Principal Investigator: Thomas Eggerman
Organization: CLINICAL CENTER
Fiscal Year: 2023
Funding agency: NIH Clinical Center
Using human SR-BI (hSR-BI) and human SR-BII (hSR-BII) transgenic mice, we have found that SR-BI and, to a lesser extent, SR-BII protect against bacterial LPS-induced lung damage:
At 20 hours after intratracheal LPS instillation, the extent of pulmonary inflammation and vascular leakage was significantly lower in hSR-BI and hSR-BII transgenic mice compared to wild type mice.
Higher bronchoalveolar lavage fluid (BALF) inflammatory cell counts and protein content, as well as lung tissue neutrophil infiltration were found in wild type mice.
In addition, there was increased pro-inflammatory cytokine production (2-3 fold) when compared to transgenic mice following IT LPS administration.
Markedly lower endotoxin levels detected in broncho-alveolar lavage of transgenic vs. wild type mice along with significantly increased BODIPY-LPS uptake were observed in lungs of hSR-BI and hSR-BII mice 20 hours after the IT LPS injection.
These results suggest that hSR-BI and hSR-BII mediated enhanced LPS clearance in the airways could represent the mechanism for their protective role against LPS-induced acute lung injury, a model of bacterial infection lung damage. In a collaboration with a U of MD group, we have published this year (PMID: 37566016) that age related accumulation of truncated oxidized phospholipids augments infectious lung injury and endothelial dysfunction.
We have begun to evaluate the role of class B scavenger receptors in the pathogenesis of SARS-CoV-2 and other viruses.. In a collaboration with NEI, we have published this year (PMID:37411618) that the low density lipoprotein receptor (LDLR) is involved with SARS-CoV-2 spike protein mediated uptake in ocular cells.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><Abscission><Acquired brain injury><Acute><Acute Lung Injury><Acute Pulmonary Injury><Antigen Presentation><Apoptotic><BODIPY><Bacterial Model><Blood Vessels><Body Tissues><Brain Injuries><Bronchioalveolar Lavage><Bronchoalveolar Lavage><Bronchoalveolar Lavage Fluid><Bronchopulmonary Lavage><CD36><CD36 gene><COVID-19 S protein><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 virus><COVID19 S protein><COVID19 spike glycoprotein><COVID19 spike protein><COVID19 virus><Cell Body><Cell Count><Cell Line><Cell Number><CellLine><Cells><Chronic Lung Injury><Chronic Pulmonary Injury><CoV-2><CoV2><Collaborations><Disease><Disorder><Endotoxins><Excision><Extirpation><Extravasation><GP3B><GP4><GPIV><HCV infection><Hepatitis C><Hepatitis C virus infection><Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted><Hepatitus C><Host Defense><Hour><Human><In Vitro><Individual><Infection><Inflammation><Inflammatory><Inflammatory Response><Injections><Injury to Kidney><Knock-out><Knockout><LDL Receptors><Leakage><Lipopolysaccharides><Lipoprotein LDL Receptors><Lipoprotein Receptor><Low Density Lipoprotein Receptor><Lung><Lung Inflammation><Lung Lavage><Lung Parenchyma><Lung Respiratory System><Lung Tissue><Lung damage><Lung infections><Mediating><Mice><Mice Mammals><Modern Man><Molecular><Murine><Mus><Neutrophil Infiltration><Neutrophil Recruitment><Neutrophilic Infiltrate><Pattern><Pattern recognition receptor><Peripheral><Phagocytosis><Phosphatides><Phospholipids><Play><Pneumonitis><Production><Protein Family><Proteins><Publishing><Pulmonary Inflammation><RNA Splicing><Receptor Protein><Removal><Resolution><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 S protein><SARS-CoV-2 pathogenesis><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV2><SARS-CoV2 S protein><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SCARB3><SR-B proteins><Sepsis><Septic Shock><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Severe acute respiratory syndrome related corona virus 2><Spillage><Splicing><Strains Cell Lines><Structure of parenchyma of lung><Surgical Removal><System><TLR protein><Tissues><Toll-Like Receptor Family Gene><Toll-like receptors><Transgenic Mice><Transgenic Organisms><Variant><Variation><Viral><Viral Diseases><Virus><Virus Diseases><Wild Type Mouse><Wuhan coronavirus><acetyl-LDL receptor><acetylated LDL receptor><age dependent><age related><blood infection><bloodstream infection><brain damage><brain-injured><bronchopulmonary lavage therapy><class B scavenger receptors><coronavirus disease 2019 S protein><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><coronavirus disease 2019 virus><coronavirus disease-19 virus><cultured cell line><cytokine><endothelial dysfunction><hCoV19><hep C><hepatitis non A non B><in vivo><infection by hepatitis c virus><kidney injury><lung injury><microbial><nCoV2><neural><non A, non B hepatitis><non-A, non-B hepatitis><overexpress><overexpression><pathogen><pathogenic virus><pulmonary><pulmonary damage><pulmonary infections><pulmonary injury><pulmonary tissue damage><pulmonary tissue injury><receptor><renal injury><resection><resolutions><scavenger receptor><severe acute respiratory syndrome coronavirus 2 pathogenesis><social role><transgenic><uptake><vascular><viral infection><viral pathogen><virus infection><virus pathogen><virus-induced disease><wildtype mouse>