The Role of the Scavenger Receptor B Family Proteins (SR-BI, SR-BII and CD36) in Infection and Sepsis

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Abstract

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 last year that the peptide L37pA protects against lung vascular endothelial dysfunction caused by truncated oxidized phospholipids through CD36 antagonism (PMID:37725486). We have published this year that CD36 is a potential therapeutic target in inflammation induced by danger-associated molecular patterns (DAMPs) (PMID: 39682740). 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 and animal studies have begun this year. 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).