Secretion of surfactant protein A and phosphatidylcholine from type II cells of human fetal lung.

Secretion of surfactant protein A and phosphatidylcholine from type II cells of human fetal lung.
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DOI:
10.1165/ajrcmb/8.5.556
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发表时间:
1993-05
影响因子:
6.4
通讯作者:
D. Froh;L. Gonzales;P. L. Ballard
D. Froh;L. Gonzales;P. L. Ballard
中科院分区:
医学1区
文献类型:
--
作者:
D. Froh;L. Gonzales;P. L. Ballard

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表面活性蛋白A(SP-A)在肺免疫防御以及肺泡表面活性膜的生成和代谢中具有重要作用。以往的研究表明,从肺组织分离的板层小体中SP-A的含量相对较低,体外快速形成表面活性膜需要外源SP-A。因此,我们验证了这一假设,即SP-A主要由II型细胞通过与板层小体分离的途径分泌。从体外培养的人胎肺外植体中分离细胞,用激素促进II型细胞分化,比较肺表面活性物质脂质和SP-A的分泌。培养细胞在48h内以接近线性的方式分泌标记的磷脂酰胆碱,酶联免疫吸附试验检测SP-A的基础分泌仅在细胞接种后12h内呈线性,在此期间细胞内没有SP-A的积聚。添加促分泌剂(佛波酯、钙离子载体和β-肾上腺素能激动剂)可刺激磷脂酰胆碱的分泌约4倍。促分泌剂对SP-A的分泌无明显影响。这些发现表明,分泌的SP-A相对少量(约10%)以板层小体形式释放。大多数SP-A是由结构性分泌释放的,可能对表面活性物质相关和非表面活性物质相关的功能都很重要。
Surfactant protein A (SP-A) appears to have a role in lung immune defense as well as generation and metabolism of the alveolar surface-active film. Previous studies indicated that lamellar bodies isolated from lung tissue had a relatively low content of SP-A and that exogenous SP-A was needed for rapid formation of a surface-active film in vitro. We therefore tested the hypothesis that SP-A was secreted from type II cells primarily by a pathway separate from lamellar bodies. Cells were isolated from explants of human fetal lung that had been cultured with hormones to promote differentiation of type II cells, and secretion of surfactant lipid and SP-A were compared. Cultured cells secreted labeled phosphatidylcholine in a nearly linear fashion for 48 h. Basal secretion of SP-A, assayed by enzyme-linked immunosorbent assay, was linear for only 12 h after plating of cells; during this time, there was no accumulation of intracellular SP-A. Addition of secretagogues (phorbol ester, calcium ionophore, and beta-adrenergic agonist) stimulated phosphatidylcholine secretion approximately 4-fold. In contrast, the secretion rate of SP-A was not significantly affected by secretagogues. These findings indicate that a relatively small amount of secreted SP-A (approximately 10%) is released with lamellar bodies. Most SP-A is released by constitutive secretion and may be important for both surfactant- and nonsurfactant-related functions.