Surfactant protein-D regulates the postnatal maturation of pulmonary surfactant lipid pool sizes
Surfactant protein-D regulates the postnatal maturation of pulmonary surfactant lipid pool sizes
复制标题
DOI：
10.1152/japplphysiol.91567.2008
复制
发表时间：
2009-05-01
影响因子：
3.3
通讯作者：
Whitsett, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Ikegami, Machiko;Grant, Shawn;Whitsett, Jeffrey A.
Ikegami M，Grant S，Korfamil T，Scheule RK，惠特塞特JA.表面活性蛋白-D调节出生后肺表面活性物质脂质池大小的成熟J Appl Physiol 106：1545-1552，2009.首次发表于2009年3月5日; doi：10.1152/japplphysiol.91567.2008。表面活性蛋白D在宿主防御和肺表面活性物质稳态中起重要作用。在SP-D缺陷（Sftpd（-/-））小鼠中，在超微结构水平上观察到的异常大表面活性剂形式被II型细胞无效吸收，导致表面活性剂池大小增加超过3倍。SP-D影响表面活性剂超微结构的机制尚不清楚。我们推测SP-D分泌后立即与表面活性剂结合，并影响表面活性剂超微结构的转化。在新生儿和成年羊肺，免疫金标记的SP-D与新分泌的表面活性剂和小聚集体表面活性剂的层状膜脂质结构，但不与管状髓鞘。由于SP-D在体外优先与磷脂酰肌醇（PI）结合，因此对PI的出生后变化进行了评估。出生后支气管肺泡灌洗液中的PI含量增加，并在2-5日龄时达到峰值，这是表面活性剂形式快速转化的时间，与表面活性剂脂质池大小的峰值相关。SP-D在体外选择性地与富含PI的脂质体相互作用，导致其裂解。同样，Sftpd（-/-）小鼠的异常表面活性剂的超微结构被纠正的SP-D或蜂毒肽，这两种肽引起的脂囊泡溶解。表面活性剂超微结构的正常转化需要SP-D优先与富含PI的新分泌的表面活性剂相互作用，导致表面活性剂脂质膜溶解，将脂质形式转化为较小的表面活性剂层状结构，这对于II型细胞吸收表面活性剂和正常表面活性剂稳态至关重要。SP-D调节新生期发生的表面活性剂池大小的急剧下降。
Ikegami M, Grant S, Korfhagen T, Scheule RK, Whitsett JA. Surfactant protein-D regulates the postnatal maturation of pulmonary surfactant lipid pool sizes. J Appl Physiol 106: 1545-1552, 2009. First published March 5, 2009; doi:10.1152/japplphysiol.91567.2008.-Surfactant protein (SP)-D plays an important role in host defense and pulmonary surfactant homeostasis. In SP-D-deficient (Sftpd(-/-)) mice, the abnormal large surfactant forms seen at the ultrastructural level are taken up inefficiently by type II cells, resulting in an over threefold increase in the surfactant pool size. The mechanisms by which SP-D influences surfactant ultrastructure are unknown. We hypothesized that SP-D binds to surfactant immediately after being secreted and influences surfactant ultrastructure conversion. In newborn and adult sheep lungs, immunogold-labeled SP-D was associated with both lamellated membranous lipid structures of newly secreted surfactant and with small aggregate surfactant but not with tubular myelin. Since SP-D preferentially binds to phosphatidylinositol (PI) in vitro, the postnatal changes in PI were assessed. PI content in the bronchoalveolar lavage fluid increased after birth and peaked at 2-5 days of age, a time of rapid conversion of surfactant forms that is associated with the peak of surfactant lipid pool size. SP-D selectively interacted with PI-rich liposomes in vitro, causing their lysis. Similarly, the abnormal surfactant ultrastructure in Sftpd(-/-) mice was corrected by the addition of SP-D or melittin, and both peptides caused lysis of lipid vesicles. The normal conversion of surfactant ultrastructure requires SP-D that preferentially interacts with PI-rich, newly secreted surfactant, causing lysis of surfactant lipid membranes, converting the lipid forms into smaller surfactant lamellated structures that are critical for surfactant uptake by type II cells and normal surfactant homeostasis. SP-D regulates the dramatic decreases in the surfactant pool size that occurs in the newborn period.