Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
Cell Host Microbe. 2010 Nov 18;8(5):445-54. doi: 10.1016/j.chom.2010.10.005.
Statins are inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent clinico-epidemiologic studies correlate patients receiving statin therapy with having reduced mortality associated with severe bacterial infection. Investigating the effect of statins on the innate immune capacity of phagocytic cells against the human pathogen Staphylococcus aureus, we uncovered a beneficial effect of statins on bacterial clearance by phagocytes, although, paradoxically, both phagocytosis and oxidative burst were inhibited. Probing instead for an extracellular mechanism of killing, we found that statins boosted the production of antibacterial DNA-based extracellular traps (ETs) by human and murine neutrophils and also monocytes/macrophages. The effect of statins to induce phagocyte ETs was linked to sterol pathway inhibition. We conclude that a drug therapy taken chronically by millions alters the functional behavior of phagocytic cells, which could have ramifications for susceptibility and response to bacterial infections in these patients.
他汀类药物是 3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶的抑制剂，该酶是胆固醇生物合成中的限速酶。最近的临床流行病学研究将接受他汀类药物治疗的患者与严重细菌感染相关的死亡率降低相关联。我们研究了他汀类药物对吞噬细胞针对人类病原体金黄色葡萄球菌的固有免疫能力的影响，发现他汀类药物对吞噬细胞的细菌清除有有益作用，尽管吞噬作用和氧化爆发都受到抑制。相反，我们探究了一种细胞外的杀伤机制，发现他汀类药物可以增强人类和鼠类中性粒细胞以及单核细胞/巨噬细胞产生的基于 DNA 的抗菌细胞外陷阱（ETs）。他汀类药物诱导吞噬细胞 ETs 的作用与固醇途径抑制有关。我们的结论是，数以百万计的人长期服用的药物治疗改变了吞噬细胞的功能行为，这可能对这些患者的细菌感染易感性和反应产生影响。
