Acute Acalculous Cholecystitis-Like Phenotype in Scavenger Receptor A Knock-Out Mice

• Published in: The Journal of surgical research 2012-05, Vol.174 (2), p.344-351
• Main Authors: Drummond, Robert, B.S, Song, Donghuan, M.D, Hawisher, Dennis, B.S, Wolf, Paul L., M.D, Vazquez, Daniel E., M.D, Nino, Diego F., M.D, Coimbra, Raul, M.D, Cauvi, David M., Ph.D, De Maio, Antonio, Ph.D
• Format: Article
• Language: English
• Subjects: Acalculous Cholecystitis - etiology; Acalculous Cholecystitis - metabolism; acute acalculous cholecystitis; Animals; Cecum - surgery; Cholesterol - blood; Disease Models, Animal; gallbladder; hypercholesterolemia; inflammation; Interleukin-10 - metabolism; Ligation; Lung - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Msr1; Phenotype; Scavenger Receptors, Class A - genetics; sepsis; Sepsis - complications; Sepsis - genetics; Sepsis - metabolism; Sra; Surgery
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2010.12.033

Background Sepsis is a major health problem in the United States that affects more than three-quarters of a million people every year. Previous studies have shown that scavenger receptor A (Sra), also known as macrophage scavenger receptor 1 (Msr1), is a modifier of interleukin 10 (IL-10) expression after injection of bacterial lipopolysaccharide (LPS). Therefore, we investigated the response to sepsis in Sra knock out mice. Materials and Methods C57BL/6J (B6) ( n = 88) and Sra (–/–) mice ( n = 88) were subjected to cecal ligation and puncture (CLP) using 18G or 16G needles, sham operation, or non-operated controls. At the end, mice were autopsied for the determination of abnormalities after the procedure. Cytokine gene expression was examined in lung and liver samples by quantitative RT-PCR (qRT-PCR), and circulating cholesterol levels were also measured. Results Sra (–/–) mice displayed an enlargement of the gallbladder after CLP that was not detected in sham or non-operated mice or in B6 mice (wild-type) after CLP. The enlarged gallbladder resembles a condition of acute acalculous cholecystitis observed in humans. Sra (–/–) mice presented high cholesterol levels in circulation as opposed to wild type B6 mice. Moreover, Sra (–/–) mice exhibited a reduction in IL-10 mRNA levels in lungs compared to wild-type B6 mice after CLP. Conclusions The development of acute acalculous cholecystitis may be the combination of pre-existing conditions, such as hypercholesterolemia associated with a defect in Sra (Msr1) and a robust inflammation induced by sepsis.