The Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
The Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Cincinnati Bronchopulmonary Dysplasia Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Ann Anat. 2023 Apr;247:152048. doi: 10.1016/j.aanat.2023.152048. Epub 2023 Jan 20.
Surfactant protein D (SP-D) is an innate host defense protein that clears infectious pathogens from the lung and regulates pulmonary host defense cells. SP-D is also detected in lower concentrations in plasma and many other non-pulmonary tissues. Plasma levels of SP-D increase during infection and other proinflammatory states; however, the source and functions of SP-D in the systemic circulation are largely unknown. We hypothesized that systemic SP-D may clear infectious pathogens and regulate host defense cells in extrapulmonary systems.
To determine if SP-D inhibited inflammation induced by systemic lipopolysaccharide (LPS), E.coli LPS was administered to mice via tail vein injection with and without SP-D and the inflammatory response was measured.
Systemic SP-D has a circulating half-life of 6 h. Systemic IL-6 levels in mice lacking the SP-D gene were similar to wild type mice at baseline but were significantly higher than wild type mice following LPS treatment (38,000 vs 29,900 ng/ml for 20 mg/kg LPS and 100,700 vs 73,700 ng/ml for 40 mg/kg LPS). In addition, treating wild type mice with purified intravenous SP-D inhibited LPS induced secretion of IL-6 and TNFα in a concentration dependent manner. Inhibition of LPS induced inflammation by SP-D correlated with SP-D LPS binding suggesting SP-D mediated inhibition of systemic LPS requires direct SP-D LPS interactions.
Taken together, the above results suggest that circulating SP-D decreases systemic inflammation and raise the possibility that a physiological purpose of increasing systemic SP-D levels during infection is to scavenge systemic infectious pathogens and limit inflammation-induced tissue injury.
表面活性蛋白 D（SP-D）是一种先天的宿主防御蛋白，可清除肺部的感染病原体并调节肺部宿主防御细胞。SP-D 也在血浆和许多其他非肺部组织中以较低浓度检测到。SP-D 水平在感染和其他促炎状态下会升高；然而，循环系统中 SP-D 的来源和功能在很大程度上尚不清楚。我们假设系统 SP-D 可能清除感染病原体并调节非肺部系统中的宿主防御细胞。
为了确定 SP-D 是否抑制全身脂多糖（LPS）引起的炎症，通过尾静脉注射向小鼠给予大肠杆菌 LPS 并同时给予和不给予 SP-D，并测量炎症反应。
系统 SP-D 的循环半衰期为 6 小时。缺乏 SP-D 基因的小鼠的全身 IL-6 水平在基线时与野生型小鼠相似，但在 LPS 处理后明显高于野生型小鼠（20mg/kg LPS 时为 38,000 与 29,900ng/ml，40mg/kg LPS 时为 100,700 与 73,700ng/ml）。此外，用纯化的静脉内 SP-D 处理野生型小鼠可浓度依赖性地抑制 LPS 诱导的 IL-6 和 TNFα 的分泌。SP-D 抑制 LPS 诱导的炎症与 SP-D-LPS 结合相关，提示 SP-D 介导的全身 LPS 抑制需要直接的 SP-D-LPS 相互作用。
综上所述，上述结果表明循环 SP-D 可降低全身炎症，并提示感染期间全身 SP-D 水平升高的生理目的可能是清除全身感染病原体并限制炎症诱导的组织损伤。
