Singhal P C, Sharma P, Garg P
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 11042, USA.
Am J Pathol. 1995 Dec;147(6):1780-9.
Patients with HIV infection often develop glomerular lesions (focal segmental glomerular sclerosis). Because mesangial expansion (enhanced mesangial cell (MC) growth and matrix accumulation) has been demonstrated to precede the development of focal segmental glomerulosclerosis, we studied the effect of the interaction between HIV-1 proteins such as gp160 envelope protein and macrophages on mesangial cell proliferation and matrix synthesis. We determined the effect of control media, serum-free macrophage supernatant (MSP), and serum-free HIV-1 gp 160 protein-treated MSP (gp 160-MSP) on the proliferation of MC and synthesis of collagen type IV (a component of mesangial matrix). MSP (20%) enhanced (P < 0.01) MC proliferation (control, 7.58 +/- 0.29 versus MSP, 9.06 +/- 0.25 x 10(4) cells/ml), whereas gp 160-MSP (20%) inhibited (P < 0.001) MC proliferation (gp160-MSP, 5.58 +/- 0.14 x 10(4) cells/ml). gp160-MSP modulated MC proliferation in a dose-dependent manner; it enhanced cell proliferation at a lower concentration but inhibited cell proliferation at a higher concentration. Anti-TGF-beta antibody attenuated the effect of gp160-MSP on MC proliferation at lower as well as higher concentrations. Bromodeoxyuridine incorporation studies also showed the modulation of MC proliferation by gp160-MSP. Interaction of other HIV proteins such as HIV-1 Gag4 and HIV-1 Tat with macrophages did not affect MC proliferation when compared with MSP alone. gp160-MSP also enhanced (P < 0.001) synthesis of type IV collagen by MC (control, 467.8 +/- 9.0; MSP, 501.0 +/- 25.0; gp160-MSP, 775.5 +/- 39.0 ng/mg protein). The effect of gp160-MSP on collagen synthesis by MC was dose-dependent. Anti-TGF-beta antibody attenuated the gp160-MSP-induced mesangial cell collagen synthesis. The present study provides a basis for speculation that macrophage-gp160 interaction products have the potential to cause expansion of the mesangium.
感染HIV的患者常出现肾小球病变（局灶节段性肾小球硬化）。由于已证实系膜扩张（系膜细胞（MC）生长增强和基质积聚）先于局灶节段性肾小球硬化的发展，我们研究了HIV-1蛋白（如gp160包膜蛋白）与巨噬细胞之间的相互作用对系膜细胞增殖和基质合成的影响。我们测定了对照培养基、无血清巨噬细胞上清液（MSP）以及无血清HIV-1 gp160蛋白处理的MSP（gp160-MSP）对MC增殖和IV型胶原（系膜基质的一种成分）合成的影响。MSP（20%）增强了（P<0.01）MC增殖（对照，7.58±0.29对MSP，9.06±0.25×10⁴个细胞/ml），而gp160-MSP（20%）抑制了（P<0.001）MC增殖（gp160-MSP，5.58±0.14×10⁴个细胞/ml）。gp160-MSP以剂量依赖方式调节MC增殖；它在较低浓度时增强细胞增殖，但在较高浓度时抑制细胞增殖。抗转化生长因子-β抗体在较低和较高浓度下均减弱了gp160-MSP对MC增殖的影响。溴脱氧尿苷掺入研究也显示了gp160-MSP对MC增殖的调节作用。与单独的MSP相比，其他HIV蛋白（如HIV-1 Gag4和HIV-1 Tat）与巨噬细胞的相互作用不影响MC增殖。gp160-MSP也增强了（P<0.001）MC合成IV型胶原的能力（对照，467.8±9.0；MSP，501.0±25.0；gp160-MSP，775.5±39.0 ng/mg蛋白）。gp160-MSP对MC胶原合成的影响是剂量依赖的。抗转化生长因子-β抗体减弱了gp160-MSP诱导的系膜细胞胶原合成。本研究为推测巨噬细胞与gp160的相互作用产物有可能导致系膜扩张提供了依据。
