Singhal P C, Gupta S, Shen Z, Schlondorff D
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Am J Physiol. 1991 Sep;261(3 Pt 2):F537-44. doi: 10.1152/ajprenal.1991.261.3.F537.
Vasoactive agents such as angiotensin (ANG) and eicosanoids can influence macromolecular deposition in the glomerular mesangium. We studied whether prostaglandin E2 (PGE2) and U-46619 (a stable analogue of thromboxane A2) could directly affect the uptake of immunoglobulin G (IgG) complexes or low-density lipoprotein (LDL) by cultured rat mesangial cells (MC). Preincubation of MC with PGE2 (10(-6) M) resulted in decreased uptake (in counts.min-1.well-1) of IgG complexes (PGE2, 2,589 +/- 72; control, 3,840 +/- 114; P less than 0.001) and LDL particles (PGE2, 23,176 +/- 1,145; control, 37,216 +/- 4,520; P less than 0.05). MC preincubated with forskolin (10(-5) M) also showed decreased uptake of IgG complexes (forskolin, 2,896 +/- 196; control, 3,840 +/- 114; P less than 0.005) and LDL particles (forskolin, 23,176 +/- 1,145; control, 37,216 +/- 4,520; P less than 0.05). In contrast, preincubation with ANG II (5 x 10(-7) M) showed significantly higher uptake of IgG complexes (ANG II, 4,475 +/- 282; control, 3,787 +/- 277; P less than 0.05) and LDL (ANG II, 48,573 +/- 1,079; control, 44,697 +/- 770; P less than 0.05). Similarly, preincubation with U-46619 (10(-6) M) resulted in significantly higher uptake of IgG complexes (U-46619, 5,370 +/- 300; control, 3,659 +/- 307; P less than 0.02) and LDL (U-46619, 48,298 +/- 1,418; control, 44,697 +/- 770; P less than 0.05). After preincubation with cyclooxygenase inhibitor meclofenamate (10(-6) M), ANG II (5 x 10(-7) M) resulted in a significantly higher uptake of IgG complexes compared with uptake by MC treated with ANG II alone (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
血管活性物质如血管紧张素(ANG)和类花生酸能够影响肾小球系膜中大分子物质的沉积。我们研究了前列腺素E2(PGE2)和U-46619(血栓素A2的稳定类似物)是否能直接影响培养的大鼠系膜细胞(MC)对免疫球蛋白G(IgG)复合物或低密度脂蛋白(LDL)的摄取。用PGE2(10⁻⁶M)预孵育MC导致IgG复合物摄取量(每分钟每孔计数)降低(PGE2组为2,589±72;对照组为3,840±114;P<0.001)以及LDL颗粒摄取量降低(PGE2组为23,176±1,145;对照组为37,216±4,520;P<0.05)。用福斯高林(10⁻⁵M)预孵育的MC也显示出IgG复合物摄取量降低(福斯高林组为2,896±196;对照组为3,840±114;P<0.005)以及LDL颗粒摄取量降低(福斯高林组为23,176±1,145;对照组为37,216±4,520;P<0.05)。相反,用ANG II(5×10⁻⁷M)预孵育显示IgG复合物摄取量显著更高(ANG II组为4,475±282;对照组为3,787±277;P<0.05)以及LDL摄取量显著更高(ANG II组为48,573±1,079;对照组为44,697±770;P<0.05)。同样,用U-46619(10⁻⁶M)预孵育导致IgG复合物摄取量显著更高(U-46619组为5,370±300;对照组为3,659±307;P<0.02)以及LDL摄取量显著更高(U-46619组为48,298±1,418;对照组为44,697±770;P<0.05)。在用环氧化酶抑制剂甲氯芬那酸(10⁻⁶M)预孵育后,与单独用ANG II处理的MC相比,ANG II(5×10⁻⁷M)导致IgG复合物摄取量显著更高(P<0.05)。(摘要截短至250字)