From the Department of Pediatrics, Division of Neonatal-Perinatal Medicine.
Department of Pediatrics, Pediatric Research Center, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX.
J Pediatr Gastroenterol Nutr. 2022 Jul 1;75(1):97-103. doi: 10.1097/MPG.0000000000003458. Epub 2022 Apr 20.
Human milk reduces the incidence of necrotizing enterocolitis (NEC). Prior studies have demonstrated that exogenous surfactant protein-A (SP-A) modulates intestinal inflammation, reduces NEC-like pathology in SP-A-deficient (SPAKO) pups, and may contribute to breast milk's immunomodulatory potential. We hypothesize that SP-A is present in milk and impacts inflammatory responses in the terminal ileum of neonatal mice.
Human milk was collected at postpartum days 1-3 and 28. Mouse milk was collected at postpartum days 1-10. SP-A was detected in milk through immunoprecipitation and western blot analysis. The impact of murine wild-type (WT) milk on SPAKO pup ileum was evaluated in a model of intestinal inflammation via cross-rearing experiments. Terminal ileum was evaluated for inflammatory cytokine and toll-like receptor 4 (TLR4) mRNA expression via quantitative real-time RT-PCR.
SP-A was detected in human milk and wild type (WT) mouse milk, but not in SPAKO mouse milk. Expression of TLR4, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was decreased in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams, with a peak effect at day of life 14. When inflammation was induced using a lipopolysaccharide-induced model of inflammation, expression of TLR4, IL-1β, IL-6, CXCL-1, and TNF-α was significantly lower in SPAKO pups reared with WT dams compared to SPAKO pups reared with SPAKO dams.
SP-A is present in human and murine milk and plays a role in lowering inflammation in murine pup terminal ileum. Both baseline inflammation and induced inflammatory responses are reduced via exposure to SP-A in milk with the effect amplified in inflammatory conditions.
人乳可降低坏死性小肠结肠炎（NEC）的发生率。先前的研究表明，外源性表面活性蛋白-A（SP-A）可调节肠道炎症，减轻 SP-A 缺陷（SPAKO）幼崽的 NEC 样病变，并可能有助于母乳的免疫调节潜力。我们假设 SP-A 存在于母乳中，并影响新生小鼠回肠的炎症反应。
在产后第 1-3 天和第 28 天收集人乳。在产后第 1-10 天收集小鼠乳。通过免疫沉淀和 Western blot 分析检测乳中的 SP-A。通过交叉饲养实验在肠道炎症模型中评估野生型（WT）小鼠乳对 SPAKO 幼崽回肠的影响。通过定量实时 RT-PCR 评估末端回肠的炎症细胞因子和 Toll 样受体 4（TLR4）mRNA 表达。
在人乳和野生型（WT）小鼠乳中检测到 SP-A，但在 SPAKO 小鼠乳中未检测到。与 SPAKO 幼崽由 SPAKO 母鼠饲养相比，由 WT 母鼠饲养的 SPAKO 幼崽的 TLR4、白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α表达降低，在生命第 14 天达到峰值。当使用脂多糖诱导的炎症模型诱导炎症时，与由 SPAKO 母鼠饲养的 SPAKO 幼崽相比，由 WT 母鼠饲养的 SPAKO 幼崽的 TLR4、IL-1β、IL-6、CXCL-1 和 TNF-α表达明显降低。
SP-A 存在于人乳和鼠乳中，可降低鼠仔回肠的炎症。通过在乳中暴露于 SP-A，无论是基础炎症还是诱导的炎症反应，都在炎症条件下放大，从而降低了炎症反应。
