Suwabe A, Panos R J, Voelker D R
Lord and Taylor Laboratory for Lung Biochemistry, Department of Medicine, National Jewish Center for Immunology, Respiratory Medicine, Denver, Colorado 80206.
Am J Respir Cell Mol Biol. 1991 Mar;4(3):264-72. doi: 10.1165/ajrcmb/4.3.264.
We examined surfactant secretion and its regulation by surfactant protein A (SP-A) in alveolar type II cells isolated from silica-treated rats to determine the role of SP-A-mediated regulatory control of phospholipid secretion in the pathogenesis of silica-induced alveolar proteinosis. Type II cells were isolated at weekly intervals for 28 d after silica or saline instillation. The maximum total binding of [125I]SP-A (internalized and surface-bound SP-A) to type II cells increased with time after silica instillation and, at 21 d, was 4-fold greater than that of type II cells isolated from saline-treated rats (272.8 +/- 42.5 and 65.4 +/- 9.8 ng/10(5) cells, respectively; P less than 0.05). Type II cells isolated from silica-treated rats showed a 2-fold increased surface binding and a 3-fold increased internalization compared to control cells. The receptor affinity for SP-A was the same for type II cells isolated from silica- and saline-treated animals. Type II cells isolated 14 d after silica instillation were separated into normotrophic and hypertrophic populations by centrifugal elutriation. Hypertrophic cells showed significantly elevated maximum total binding compared to normotrophic cells. The secretion of [3H]phosphatidylcholine [( 3H]PC) by type II cells from silica- and saline-treated animals was also compared. Type II cells from silica-treated animals showed lower basal and tetradecanoyl phorbol acetate (TPA)-stimulated [3H]PC secretion than cells from saline-treated animals at each time point after instillation. SP-A inhibited TPA-stimulated [3H]PC secretion similarly in type II cells isolated after either silica or saline instillation.(ABSTRACT TRUNCATED AT 250 WORDS)
我们检测了从经二氧化硅处理的大鼠分离出的II型肺泡细胞中表面活性物质的分泌及其受表面活性蛋白A（SP-A）的调节情况，以确定SP-A介导的磷脂分泌调节控制在二氧化硅诱导的肺泡蛋白沉积症发病机制中的作用。在二氧化硅或生理盐水注入后，每周间隔分离II型细胞，持续28天。[125I]SP-A（内化和表面结合的SP-A）与II型细胞的最大总结合量在二氧化硅注入后随时间增加，在21天时，比从生理盐水处理的大鼠分离出的II型细胞高4倍（分别为272.8±42.5和65.4±9.8 ng/10(5)细胞；P<0.05）。与对照细胞相比，从经二氧化硅处理的大鼠分离出的II型细胞表面结合增加了2倍，内化增加了3倍。从经二氧化硅和生理盐水处理的动物分离出的II型细胞对SP-A的受体亲和力相同。在二氧化硅注入14天后分离出的II型细胞通过离心淘析分为正常营养型和肥大细胞群。肥大细胞与正常营养型细胞相比，最大总结合量显著升高。还比较了经二氧化硅和生理盐水处理的动物的II型细胞分泌[3H]磷脂酰胆碱[（3H]PC）的情况。在注入后的每个时间点，经二氧化硅处理的动物的II型细胞的基础和十四烷酰佛波醇乙酸酯（TPA）刺激的[3H]PC分泌均低于经生理盐水处理的动物的细胞。在经二氧化硅或生理盐水注入后分离出的II型细胞中，SP-A对TPA刺激的[3H]PC分泌的抑制作用相似。（摘要截短于250字）
