Class B Scavenger Receptors BI and BII Protect against LPS-Induced Acute Lung Injury in Mice by Mediating LPS

• Published in: Infection and immunity 2021-09, Vol.89 (10), p.e0030121
• Main Authors: Baranova, Irina N, Bocharov, Alexander V, Vishnyakova, Tatyana G, Chen, Zhigang, Birukova, Anna A, Ke, Yunbo, Hu, Xuzhen, Yuen, Peter S T, Star, Robert A, Birukov, Konstantin G, Patterson, Amy P, Eggerman, Thomas L
• Format: Article
• Language: English
• Subjects: A549 Cells; Acute Lung Injury - chemically induced; Acute Lung Injury - metabolism; Animals; Bronchoalveolar Lavage Fluid; Cell Line, Tumor; Cytokines - metabolism; Disease Models, Animal; Endotoxemia - metabolism; Host Response and Inflammation; Host-Microbial Interactions; Humans; Inflammation - immunology; Lipopolysaccharides - pharmacology; Lysosomal Membrane Proteins - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neutrophils - metabolism; Receptors, Scavenger - metabolism; Scavenger Receptors, Class B - metabolism; Sepsis - metabolism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00301-21

Recent studies suggest an anti-inflammatory protective role for class B scavenger receptor BI (SR-BI) in endotoxin-induced inflammation and sepsis. Other data, including ours, provide evidence for an alternative role of SR-BI, facilitating bacterial and endotoxin uptake and contributing to inflammation and bacterial infection. Enhanced endotoxin susceptibility of SR-BI-deficient mice due to their anti-inflammatory glucocorticoid deficiency complicates the understanding of SR-BI's role in endotoxemia/sepsis, calling for the use of alternative models. In this study, using human SR-BI (hSR-BI) and hSR-BII transgenic mice, we found that SR-BI and, to a lesser extent, its splicing variant SR-BII protect against LPS-induced lung damage. At 20 h after intratracheal LPS instillation, the extent of pulmonary inflammation and vascular leakage was significantly lower in hSR-BI and hSR-BII transgenic mice than in wild-type mice. Higher bronchoalveolar lavage fluid (BALF) inflammatory cell count and protein content and lung tissue neutrophil infiltration found in wild-type mice were associated with markedly (2 to 3 times) increased proinflammatory cytokine production compared to these parameters in transgenic mice following LPS administration. The markedly lower endotoxin levels detected in BALF of transgenic versus wild-type mice and the significantly increased BODIPY-LPS uptake observed in lungs of hSR-BI and hSR-BII mice 20 h after the i.t. LPS injection suggest that hSR-BI- and hSR-BII-mediated enhanced LPS clearance in the airways could represent the mechanism of their protective role against LPS-induced acute lung injury.