LIPOPOLYSACCHARIDE INDUCES PROSTAGLANDIN-H SYNTHASE-2 PROTEIN AND MESSENGER-RNA IN HUMAN ALVEOLAR MACROPHAGES AND BLOOD MONOCYTES
LIPOPOLYSACCHARIDE INDUCES PROSTAGLANDIN-H SYNTHASE-2 PROTEIN AND MESSENGER-RNA IN HUMAN ALVEOLAR MACROPHAGES AND BLOOD MONOCYTES
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DOI：
10.1172/jci116971
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发表时间：
1994-01-01
影响因子：
15.9
通讯作者：
HUNNINGHAKE, GW
中科院分区：
文献类型：
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作者：
HEMPEL, SL;MONICK, MM;HUNNINGHAKE, GW
我们和其他人以前已经证明，人肺泡巨噬细胞产生更多的PGE，响应脂多糖（LPS）比血液单核细胞。我们假设这一观察结果是由于与单核细胞相比，巨噬细胞中前列腺素H合酶-2（PGHS-2）酶质量的增加更大。为了评估这一假设，肺泡巨噬细胞和血液单核细胞从健康的非吸烟志愿者。在0至10 μ g/ml LPS存在下培养细胞。LPS诱导人肺泡巨噬细胞合成大量新的75-kD蛋白，单核细胞合成较少。这种蛋白质的合成需要超过6小时，并在24至48小时达到峰值;该蛋白质与针对小鼠PGHS-2制备的抗PGHS-2抗体反应。与蛋白质的合成相关的是，与单核细胞相比，肺泡巨噬细胞的LPS刺激和花生四烯酸刺激的PGE合成显著增加。未暴露于LPS的细胞仅含有PGHS-1，并且在培养期间或响应于外源性花生四烯酸而合成非常少的PGE。LPS诱导的mRNA与PGHS-2 mRNA的人cDNA探针杂交，与这种新蛋白的产生平行产生，并且与血液单核细胞相比，肺泡巨噬细胞产生的量要大得多。这种mRNA在未暴露于LPS的细胞中检测不到。相反，两种类型的细胞都含有mRNA，其与PGHS-1的cDNA探针杂交。这种mRNA在对LPS的反应中没有增加。LPS对PGHS-1蛋白也无影响。这些数据表明，人肺泡巨噬细胞和血液单核细胞中的PGE 1合成与细胞中PGHS-2的质量相关。我们的结论是，更大的能力，巨噬细胞合成PGE，在响应LPS是由于更大的合成PGHS-2的巨噬细胞。
We and others have previously demonstrated that human alveolar macrophages produce more PGE, in response to lipopolysaccharide (LPS) than do blood monocytes. We hypothesized that this observation was due to a greater increase in prostaglandin H synthase-2 (PGHS-2) enzyme mass in the macrophage compared to the monocyte. To evaluate this hypothesis, alveolar macrophages and blood monocytes were obtained from healthy nonsmoking volunteers. The cells were cultured in the presence of 0 to 10 mu g/ml LPS. LPS induced the synthesis of large amounts of a new 75-kD protein in human alveolar macrophages, and a lesser amount in monocytes. Synthesis of this protein required more than 6 h and peaked in 24 to 48 h; the protein reacted with an anti-PGHS-2 antibody prepared against mouse PGHS-2. Associated with synthesis of the protein was a marked increase in LPS-stimulated and arachidonic acid-stimulated synthesis of PGE, by alveolar macrophages compared to monocytes. Cells not exposed to LPS contained only PGHS-1 and synthesized very little PGE, during culture or in response to exogenous arachidonic acid. An LPS-induced mRNA, which hybridized to a human cDNA probe for PGHS-2 mRNA, was produced in parallel with production bf this new protein and was produced in much greater amounts by alveolar macrophages compared to blood monocytes. This mRNA was not detectable in cells not exposed to LPS. In contrast, both types of cells contain mRNA, which hybridizes to a cDNA probe for PGHS-1. This mRNA did not increase in response to LPS. LPS also had no effect on PGHS-1 protein. These data demonstrate that PGE, synthesis in human alveolar macrophages and blood monocytes correlates to the mass of PGHS-2 in the cell. We conclude that the greater ability of the macrophage to synthesize PGE, in response to LPS is due to greater synthesis of PGHS-2 by the macrophage.