Rooney S A, Gobran L I, Umstead T M, Phelps D S
Department of Pediatrics, Yale University, School of Medicine, New Haven, Connecticut 06510.
Am J Physiol. 1993 Dec;265(6 Pt 1):L586-90. doi: 10.1152/ajplung.1993.265.6.L586.
Secretion of surfactant phosphatidylcholine has been extensively studied and there is evidence that it is a regulated process that can be influenced by a variety of physiological factors and pharmacological agents. In contrast, secretion of the major surfactant protein, surfactant protein A (SP-A), has been investigated to much lesser extent. It is not known whether SP-A secretion is constitutive or regulated and, if regulated, whether its regulation is similar to that of phosphatidylcholine. To address those questions we measured SP-A secretion in primary cultures of type II pneumocytes under conditions identical to those used to study phosphatidylcholine secretion. Freshly isolated cells from adult rats were cultured overnight, washed, and then incubated in fresh medium in the presence and absence of surfactant phospholipid secretagogues. As previously reported for phosphatidylcholine, SP-A secretion was linear with time for up to 4 h. However, the rate of SP-A secretion, approximately 6% of total SP-A (cells+medium) released into the medium per hour, was more than sixfold greater than that of the lipid. Although freshly isolated cells contained 70% more SP-A than cells that were cultured overnight, the rate of SP-A secretion was not significantly different. Secretion of SP-A by freshly isolated or cultured type II cells was not increased by a combination of ATP, terbutaline, the adenosine A2 receptor agonist 5'(N-ethylcarboxyamido)adenosine, 12-O-tetradecanoylphorbol-13-acetate, and ionomycin at concentrations that optimally stimulated phosphatidylcholine secretion. We conclude that secretion of the major lipid and protein components of surfactant are independently regulated.
表面活性物质磷脂酰胆碱的分泌已得到广泛研究，有证据表明这是一个可受多种生理因素和药物影响的调节过程。相比之下，主要表面活性物质蛋白——表面活性物质蛋白A（SP - A）的分泌研究程度要小得多。目前尚不清楚SP - A的分泌是组成性的还是受调节的，如果是受调节的，其调节方式是否与磷脂酰胆碱类似。为了解决这些问题，我们在与研究磷脂酰胆碱分泌相同的条件下，测量了II型肺细胞原代培养物中SP - A的分泌。从成年大鼠新鲜分离的细胞培养过夜，洗涤后，在有和没有表面活性物质磷脂分泌刺激物的情况下，于新鲜培养基中孵育。如先前关于磷脂酰胆碱的报道，SP - A的分泌在长达4小时内与时间呈线性关系。然而，SP - A的分泌速率，即每小时释放到培养基中的总SP - A（细胞+培养基）的约6%，比脂质的分泌速率高出六倍多。尽管新鲜分离的细胞所含的SP - A比培养过夜的细胞多70%，但SP - A的分泌速率并无显著差异。新鲜分离或培养的II型细胞分泌SP - A，在能最佳刺激磷脂酰胆碱分泌的ATP、特布他林、腺苷A2受体激动剂5'（N - 乙基甲酰胺基）腺苷、12 - O - 十四酰佛波醇 - 13 - 乙酸酯和离子霉素的组合作用下并未增加。我们得出结论，表面活性物质的主要脂质和蛋白质成分的分泌是独立调节的。
