Division of Pediatrics and Neonatal Critical Care, "A.Béclère" Medical Center, South Paris University Hospitals, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France.
Physiopathology and Therapeutic Innovation Unit-INSERM U999, South Paris-Saclay University, Paris, France.
Am J Physiol Lung Cell Mol Physiol. 2020 Jul 1;319(1):L95-L104. doi: 10.1152/ajplung.00462.2019. Epub 2020 May 13.
Secreted phospholipase A hydrolyzes surfactant phospholipids and is crucial for the inflammatory cascade; preterm neonates are treated with exogenous surfactant, but the interaction between surfactant and phospholipase is unknown. We hypothesize that this interplay is complex and the enzyme plays a relevant role in neonates needing surfactant replacement. We aimed to: ) identify phospholipases A isoforms expressed in preterm lung; ) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and ) verify whether phospholipase A is linked to respiratory outcomes. In bronchoalveolar lavages of preterm neonates, we measured enzyme activity (alone or with inhibitors), enzyme subtypes, surfactant protein-A, and inflammatory mediators. Surfactant function and phospholipid profile were also tested. Urea ratio was used to obtain epithelial lining fluid concentrations. Follow-up data were prospectively collected. Subtype-IIA is the main phospholipase isoform in preterm lung, although subtype-IB may be significantly expressed. Neonates needing surfactant retreatment have higher enzyme activity ( = 0.021) and inflammatory mediators ( always ≤ 0.001) and lower amounts of phospholipids ( always < 0.05). Enzyme activity was inversely correlated to surfactant adsorption (ρ = -0.6; = 0.008; adjusted = 0.009), total phospholipids (ρ = -0.475; = 0.05), and phosphatidylcholine (ρ = -0.622; = 0.017). Exogenous surfactant significantly reduced global phospholipase activity ( < 0.001) and subtype-IIA ( = 0.005) and increased dioleoylphosphatidylglycerol ( < 0.001) and surfactant adsorption ( < 0.001). Enzyme activity correlated with duration of ventilation (ρ = 0.679, = 0.005; adjusted = 0.04) and respiratory morbidity score at 12 mo postnatal age (τ = 0.349, = 0.037; adjusted = 0.043) but was not associated with mortality, bronchopulmonary dysplasia, or other long-term respiratory outcomes.
分泌型磷脂酶 A 水解表面活性剂磷脂，对炎症级联反应至关重要；早产儿接受外源性表面活性剂治疗，但表面活性剂与磷脂酶的相互作用尚不清楚。我们假设这种相互作用很复杂，并且该酶在需要表面活性剂替代的新生儿中发挥相关作用。我们的目的是：）鉴定早产儿肺中表达的磷脂酶 A 同工型；）研究酶在表面活性剂再处理和功能中的作用以及外源性表面活性剂对酶系统的影响；并）验证磷脂酶 A 是否与呼吸结局相关。在早产儿的支气管肺泡灌洗液中，我们测量了酶活性（单独或与抑制剂一起）、酶亚型、表面活性蛋白-A 和炎症介质。还测试了表面活性剂功能和磷脂谱。尿素比用于获得上皮衬里液浓度。前瞻性收集随访数据。亚型-IIA 是早产儿肺中主要的磷脂酶同工型，尽管亚型-IB 可能表达明显。需要表面活性剂再处理的新生儿的酶活性（ = 0.021）和炎症介质（始终≤0.001）较高，而磷脂含量较低（始终<0.05）。酶活性与表面活性剂吸附呈负相关（ρ =-0.6； = 0.008；调整后 = 0.009），与总磷脂（ρ =-0.475； = 0.05）和磷脂酰胆碱（ρ =-0.622； = 0.017）呈负相关。外源性表面活性剂显著降低了总磷脂酶活性（ < 0.001）和亚型-IIA（ = 0.005），增加了二油酰基磷脂酰甘油（ < 0.001）和表面活性剂吸附（ < 0.001）。酶活性与通气时间（ρ = 0.679， = 0.005；调整后 = 0.04）和 12 个月后呼吸发病率评分（τ = 0.349， = 0.037；调整后 = 0.043）呈正相关，但与死亡率、支气管肺发育不良或其他长期呼吸结局无关。
