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Principal Investigator: Thomas Eggerman
Organization: CLINICAL CENTER
Fiscal Year: 2024
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 (PMID: 37566016) that age related accumulation of truncated oxidized phospholipids augments infectious lung injury and endothelial dysfunction. In addition with this group, we published this year that the peptide L37pA protects against lung vascular endothelial dysfunction caused by truncated oxidized phospholipids through CD36 antagonism (PMID:37725486).
We have begun to evaluate the role of class B scavenger receptors in the pathogenesis of SARS-CoV-2 and other viruses. In collaboration with NIAID, this role is being characterized including a candidate therapeutic. In a collaboration with NEI, we have published (PMID:37411618) that the low density lipoprotein receptor (LDLR) is involved with SARS-CoV-2 spike protein mediated uptake in ocular cells.
Regarding coronary artery disease, in collaboration with NHLBI, we have found an association of oxidized apoB and ApoA-I with high-risk coronary plaque (PMID: 37698922).
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 Lung Injury><Acute Pulmonary Injury><Antigen Presentation><Apo A-1><Apo A-I><Apo A1><Apo AI><Apo-B><ApoA-1><ApoA-I><ApoB><Apolipoprotein A-1><Apolipoprotein A-I><Apolipoprotein A1><Apolipoprotein AI><Apolipoproteins B><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><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID-19 virus><COVID19 virus><Cell Body><Cell Count><Cell Line><Cell Number><CellLine><Cells><Chronic Lung Injury><Chronic Pulmonary Injury><CoV-2><CoV2><Collaborations><Coronary Arteriosclerosis><Coronary Artery Disease><Coronary Artery Disorder><Coronary Atherosclerosis><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><NHLBI><NIAID><National Heart, Lung, and Blood Institute><National Institute of Allergy and Infectious Disease><Neutrophil Infiltration><Neutrophil Recruitment><Neutrophilic Infiltrate><Pattern><Pattern recognition receptor><Peptides><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><SARS-CoV-2 S protein><SARS-CoV-2 pathogenesis><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV2><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 associated><age correlated><age dependent><age linked><age related><age specific><antagonism><antagonist><atherosclerotic coronary disease><blood infection><bloodstream infection><brain damage><brain-injured><bronchopulmonary lavage therapy><class B scavenger receptors><coronary arterial disease><coronary plaque><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><emergent virus><emerging virus><endothelial dysfunction><hCoV19><hep C><hepatitis non A non B><high risk><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><spike proteins on SARS-CoV-2><therapeutic candidate><transgenic><uptake><vascular><vascular endothelial dysfunction><viral emergence><viral infection><viral pathogen><virus infection><virus pathogen><virus-induced disease><wildtype mouse>