Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D
Altered surfactant homeostasis and alveolar type II cell morphology in mice lacking surfactant protein D
复制标题
DOI：
10.1073/pnas.95.20.11869
复制
发表时间：
1998-09-29
影响因子：
11.1
通讯作者：
Hawgood, S
中科院分区：
文献类型：
--
作者：
Botas, C;Poulain, F;Hawgood, S
表面活性蛋白D（SurfactantProteinD，SP-D）是肺泡内发现的两种胶原聚集蛋白之一，与其他胶原聚集蛋白具有同源性，其潜在功能包括天然免疫和表面活性物质代谢。突变SP-D等位基因杂合子小鼠的SP-D浓度约为野生型的50%，但无其他明显的表型异常。完全缺乏SP-D的小鼠在7个月内是健康的，但肺泡腔中的表面活性剂脂质、SP-A和SP-B进行性积累。到8周时，肺泡磷脂库比野生型同窝仔高8倍。在无效小鼠中也有10倍的肺泡巨噬细胞积聚，许多巨噬细胞外观上是多核和泡沫状的。无效小鼠的II型细胞增生，并含有巨大的板层体。表面活性物质稳态的这些改变与表面活性物质表面活性、出生后呼吸功能或存活率的可检测变化无关。在SP-D缺陷小鼠中的发现表明SP-D在表面活性剂稳态中的作用。
Surfactant protein D (SP-D) is one of two collectins found in the pulmonary alveolus, On the basis of homology with other collectins, potential functions for SP-D include roles in innate immunity and surfactant metabolism, The SP-D gene was disrupted in embryonic stem cells by homologous recombination to generate mice deficient in SP-D, Mice heterozygous for the mutant SP-D allele had SP-D concentrations that were approximately 50% wild type but no other obvious phenotypic abnormality. Mice totally deficient in SP-D were healthy to 7 months but had a progressive accumulation of surfactant lipids, SP-A, and SP-B in the alveolar space. By 8 weeks the alveolar phospholipid pool was 8-fold higher than wild-type littermates. There was also a 10-fold accumulation of alveolar macrophages in the null mice, and many macrophages were both multinucleated and foamy in appearance. Type II cells in the null mice were hyperplastic and contained giant lamellar bodies. These alterations in surfactant homeostasis were not associated with detectable changes in surfactant surface activity, postnatal respiratory function, or survival. The findings in the SP-D-deficient mice suggest a role for SP-D in surfactant homeostasis.