Department of Surgery and.
Anesthesia, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
JCI Insight. 2021 Oct 22;6(20):e150813. doi: 10.1172/jci.insight.150813.
Infection is a common complication of major trauma that causes significantly increased morbidity and mortality. The mechanisms, however, linking tissue injury to increased susceptibility to infection remain poorly understood. To study this relationship, we present a potentially novel murine model in which a major liver crush injury is followed by bacterial inoculation into the lung. We find that such tissue trauma both impaired bacterial clearance and was associated with significant elevations in plasma heme levels. While neutrophil (PMN) recruitment to the lung in response to Staphylococcus aureus was unchanged after trauma, PMN cleared bacteria poorly. Moreover, PMN show > 50% less expression of TLR2, which is responsible, in part, for bacterial recognition. Administration of heme effectively substituted for trauma. Finally, day 1 trauma patients (n = 9) showed similar elevations in free heme compared with that seen after murine liver injury, and circulating PMN showed similar TLR2 reduction compared with volunteers (n = 6). These findings correlate to high infection rates.
感染是严重创伤的常见并发症，会显著增加发病率和死亡率。然而，将组织损伤与易感染性增加联系起来的机制仍知之甚少。为了研究这种关系，我们提出了一种潜在的新型小鼠模型，其中肝脏严重挤压伤后将细菌接种到肺部。我们发现，这种组织创伤既损害了细菌清除能力，又与血浆血红素水平显著升高有关。虽然创伤后对金黄色葡萄球菌的中性粒细胞（PMN）向肺部的募集没有改变，但PMN清除细菌的能力很差。此外，PMN 表达 TLR2 的水平降低了 >50%，而 TLR2 部分负责细菌识别。血红素的给药有效地替代了创伤。最后，创伤后第 1 天的患者（n=9）的游离血红素水平与小鼠肝损伤后观察到的水平相似，而循环 PMN 的 TLR2 水平与志愿者（n=6）相似。这些发现与高感染率相关。
