Endotoxin stimulates platelet-derived growth factor production from cultured human pulmonary endothelial cells.
Endotoxin stimulates platelet-derived growth factor production from cultured human pulmonary endothelial cells.
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内毒素刺激培养的人肺内皮细胞产生血小板衍生生长因子。
DOI：
10.1152/ajplung.1989.257.2.l65
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Kern,JA
中科院分区：
文献类型：
--
作者：
Albelda,SM;Elias,JA;Levine,EM;Kern,JA
革兰氏阴性细菌细胞壁产物（内毒素）与内皮细胞的相互作用被认为是革兰氏阴性脓毒症的许多损害性表现的原因。由于培养的人内皮细胞对内毒素的直接细胞毒性作用具有相对抗性，因此内毒素的许多全身性作用可能是由刺激内皮细胞产生生物活性介质引起的，所述生物活性介质然后可以作用于靶细胞，例如平滑肌细胞、成纤维细胞和白细胞。我们假设一种这样的内皮细胞衍生介质可能是血小板衍生生长因子（PDGF），一种引起间充质细胞增殖，白细胞，成纤维细胞和平滑肌细胞趋化性和血管收缩的蛋白质。因此，我们研究了内毒素对培养的成人肺动脉内皮细胞产生PDGF样蛋白的影响。内毒素暴露24小时导致PDGF B链（c-sis）编码mRNA的稳态水平增加3倍，释放到培养基中的新合成PDGF的量增加2 - 3倍，通过[35 S]甲硫氨酸标记蛋白与抗PDGF抗血清的免疫沉淀测定。我们的结论是，人肺动脉内皮细胞在培养刺激产生的PDGF mRNA的量增加，并释放PDGF样蛋白暴露于内毒素后。人内皮细胞释放PDGF样蛋白的增加可能在炎症浸润、血管痉挛和成纤维细胞增殖中发挥作用，这些是宿主对内毒素反应的特征。
The interaction of Gram-negative bacterial cell wall products (endotoxins) with endothelial cells is thought to be responsible for many of the damaging manifestations of Gram-negative sepsis. Because cultured human endothelial cells are relatively resistant to the direct cytotoxic actions of endotoxin, it is possible that many of the systemic effects of endotoxin may be caused by stimulation of endothelial cells to produce biologically active mediators which could then act on targets such as smooth muscle cells, fibroblasts, and leukocytes. We hypothesized that one such endothelial cell-derived mediator could be platelet-derived growth factor (PDGF), a protein that causes proliferation of mesenchymal cells, chemotaxis of leukocytes, fibroblasts and smooth muscle cells, and vasoconstriction. We therefore examined the effect of endotoxin on PDGF-like protein production by cultured adult human pulmonary artery endothelial cells. Twenty-four hours of endotoxin exposure resulted in a threefold increase in the steady-state levels of mRNA coding for PDGF B-chain (c-sis) and a two- to threefold increase in the amount of newly synthesized PDGF released into the media, as measured by immunoprecipitation of [35S]methionine-labeled protein with anti-PDGF antiserum. We conclude that human pulmonary artery endothelial cells in culture are stimulated both to produce increased amounts of PDGF mRNA and to release PDGF-like protein after exposure to endotoxin. This increased release of PDGF-like protein by human endothelial cells may play a role in the inflammatory infiltrate, vasospasm, and fibroblast proliferation that characterize the host response to endotoxin.