Leukotriene C4 binds to human glomerular epithelial cells and promotes their proliferation in vitro.
Leukotriene C4 binds to human glomerular epithelial cells and promotes their proliferation in vitro.
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白三烯 C4 与人肾小球上皮细胞结合并促进其体外增殖。
DOI：
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发表时间：
1985
影响因子：
15.9
通讯作者：
R. Ardaillou
中科院分区：
文献类型：
--
作者：
L. Baud;J. Sraer;J. Pérez;M. Nivez;R. Ardaillou
在人类和实验性肾小球肾炎中，肾小球细胞过多是由巨噬细胞积聚和常驻肾小球细胞增殖引起的。最近发现的巨噬细胞源性因子，刺激肾小球系膜和上皮细胞增殖表明，这些因素可能有助于细胞过多。为了确定这种巨噬细胞衍生的生长因子的身份，我们研究了从巨噬细胞和白细胞释放的产物白三烯（LT）对培养的人肾小球上皮细胞增殖的影响。[3H]胸苷掺入的剂量依赖性（1 - 100 nM）刺激，细胞增殖的指数，在与硫肽LT，LTC4和LTD 4孵育的细胞中观察到，但不是与LTB 4。在100 nM LTC4和LTD4下，响应值分别为对照值的248和172%。LTC4的这种作用被FPL 55712消除。随后的结合研究表明，肾小球上皮细胞具有LTC4的特异性受体。[3H] LTC4在8 ℃下快速结合细胞。孵育40分钟后出现平台期。最大特异性结合为总结合的70 - 90%。特异性结合是完全可逆的添加过量的未标记的LTC4。在两种浓度的[3H] LTC4和单一浓度的[3H] LTC4和浓度递增的未标记LTC4之间的竞争的时程关联斜率分析允许分别计算220和217 nM的解离常数（Kd）。LTD 4和LTE 4均表现出比LTC 4高至少一个数量级的ED 50值。因此，我们的研究结果表明，LTC4结合肾小球上皮细胞的特异性受体，促进这些细胞的增殖，并可能有助于肾小球肾炎中发现的上皮细胞过多。
In human and experimental glomerulonephritis, glomerular hypercellularity results both from accumulation of macrophages and proliferation of resident glomerular cells. The recent identification of macrophage-derived factors that stimulate mesangial and epithelial cell proliferation suggests that these factors might contribute to the hypercellularity. To determine the identity of such macrophage-derived growth factors, we studied the effect of leukotrienes (LTs), products that are released from macrophages and leukocytes, on proliferation of human glomerular epithelial cells in culture. Dose-dependent (1-100 nM) stimulation of [3H]thymidine incorporation, an index of cell proliferation, was observed in cells incubated with the sulfidopeptide LTs, LTC4 and LTD4, but not with LTB4. The response was 248 and 172% of control values at 100 nM LTC4 and LTD4, respectively. This effect of LTC4 was abolished by FPL 55712. Subsequent binding studies demonstrated that glomerular epithelial cells possess specific receptors for LTC4. [3H]LTC4 bound rapidly at 8 degrees C to the cells. There was a plateau after 40 min incubation. Maximum specific binding was 70-90% of total binding. Specific binding was totally reversible with addition of an excess of unlabeled LTC4. Analysis of time-course association slopes at two concentrations of [3H]LTC4 and of the competition between a single concentration of [3H]LTC4 and increasing concentrations of unlabelled LTC4 allowed calculation of dissociation constants (Kd) of 220 and 217 nM, respectively. Both LTD4 and LTE4 exhibited ED50 values that were at least one order of magnitude higher than for LTC4. Thus, our findings suggest that LTC4 binds to specific receptors of glomerular epithelial cells, promotes proliferation of these cells, and could contribute to epithelial hypercellularity found in glomerulonephritis.
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影响因子：
2.9
作者：
Mathews,WR;Rokach,J;Murphy,RC
通讯作者：
Murphy,RC
影响因子：
15.9
作者：
HOLDSWORTH, SR;NEALE, TJ;WILSON, CB
通讯作者：
WILSON, CB
体外人肾小球细胞：分离和表征。
影响因子：
0.9
作者：
Striker,GE;Killen,PD;Farin,FM
通讯作者：
Farin,FM
白三烯 C 促进人内皮细胞合成前列环素。
DOI：
10.1073/pnas.80.13.4109
发表时间：
1983
影响因子：
11.1
作者：
Cramer,EB;Pologe,L;Pawlowski,NA;Cohn,ZA;Scott,WA
通讯作者：
Scott,WA
平滑肌细胞系上白三烯 C4 的特异性受体。
DOI：
10.1172/jci111109
发表时间：
1983
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Krilis,S;Lewis,RA;Corey,EJ;Austen,KF
通讯作者：
Austen,KF