PULMONARY ALVEOLAR TYPE-II EPITHELIAL-CELLS SYNTHESIZE AND SECRETE PROTEINS OF THE CLASSICAL AND ALTERNATIVE COMPLEMENT PATHWAYS
PULMONARY ALVEOLAR TYPE-II EPITHELIAL-CELLS SYNTHESIZE AND SECRETE PROTEINS OF THE CLASSICAL AND ALTERNATIVE COMPLEMENT PATHWAYS
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DOI：
10.1172/jci113472
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发表时间：
1988-05-01
影响因子：
15.9
通讯作者：
MASON, RJ
中科院分区：
文献类型：
--
作者：
STRUNK, RC;EIDLEN, DM;MASON, RJ
血清补体系统是炎症反应的主要介质。两种补体蛋白，第三（C3）和第五（C5）组分，是强效炎症分子C3a和C5a的前体。C5a具有强的趋化活性，在肺部炎症中起积极作用。我们目前的证据表明，几种补体蛋白，包括C5，在肺泡II型上皮细胞中的肺局部合成。正常小鼠的肺组织合成并分泌与小鼠血清中C5蛋白相似的C5蛋白，而C5缺陷小鼠的肺组织则没有。正常和C5缺陷小鼠的肺组织合成C3。大鼠肺组织合成并分泌C5，以及C2、C4、C3和因子B。培养的II型细胞（95%的II型细胞，5%的巨噬细胞）定期合成所有这些蛋白质。相比之下，单独培养的巨噬细胞合成大量的C2和因子B，在一些实验中合成C3和C4，但从不合成C5。大鼠细胞合成的C5略大于血清C5（200 kD与180 kD相比），并且没有加工成血清中可见的双链分子。大鼠肺组织和纯化的II型细胞含有C5 mRNA，其分子量与大鼠肝脏和小鼠肺和肝脏中的C5 mRNA相同。人类II型细胞也合成C5，以及C2、C4、C3和因子B。人肺巨噬细胞仅合成C2、因子B，并且在一些实验中合成C3。肺泡壁细胞中补体蛋白的合成可能为肺部炎症反应提供了这些蛋白的局部来源。补体蛋白的局部合成可以独立于肝脏中的合成而受到调节。
The serum complement system is a major mediator of inflammation reactions. Two of the complement proteins, the third (C3) and fifth (C5) components, are precursors of potent phlogistic molecules, C3a and C5a. C5a has potent chemotactic activity and plays an active role in pulmonary inflammation. We present evidence suggesting that several complement proteins, including C5, are synthesized locally in the lung in alveolar type II epithelial cells. Lung tissue from normal mice synthesized and secreted C5 protein similar to the C5 protein in mouse serum, whereas lung tissue from C5-deficient mice did not. Lung tissues from both normal and C5-deficient mice synthesized C3. Rat lung tissue synthesized and secreted C5, as well as C2, C4, C3, and factor B. Cultures of type II cells (95% type II cells, 5% macrophages) regularly synthesized all these proteins. In contrast, cultures of macrophages alone synthesized large amounts of C2 and factor B, and in some experiments C3 and C4, but never C5. The C5 synthesized by the rat cells was slightly larger than serum C5 (200 kD compared with 180 kD) and was not processed to the two-chain molecule seen in serum. Rat lung tissue and purified type II cells contained C5 mRNA with the same molecular mass as the C5 mRNA in rat liver and in mouse lung and liver. Human type II cells also synthesized C5, as well as C2, C4, C3, and factor B. Human pulmonary macrophages synthesized only C2, factor B, and, in some experiments, C3. Synthesis of complement proteins in cells that line the alveolar wall may provide a local source of these proteins for inflammatory responses in the lung. Local synthesis of complement proteins could be regulated independently of the synthesis in the liver.