Bergamini A, Perno C F, Dini L, Capozzi M, Pesce C D, Ventura L, Cappannoli L, Falasca L, Milanese G, Caliò R
Department of Public Health, University of Rome Tor Vergata, Italy.
Blood. 1994 Nov 15;84(10):3405-12.
The effects of macrophage colony-stimulating factor (M-CSF) on CD4 receptor expression, susceptibility to human immunodeficiency virus type 1 (HIV) infection, and anti-HIV activity of dextran sulfate and soluble-CD4 were studied in cultured, human primary macrophages. M-CSF stimulated macrophage cells to express the CD4 receptor, and this resulted in an increase of both the number of CD4+ cells and the density of the receptor on the cell surface. M-CSF also significantly enhanced the susceptibility of macrophage cells to HIV infection. Interestingly, the anti-HIV activity of dextran sulfate and soluble-CD4 (two compounds that interfere with HIV-CD4 binding with different mechanisms) was reduced 100-fold and fivefold, respectively, in M-CSF-treated macrophages. Human blood concentrations of M-CSF are reported to be similar to those used in this work (1,000 U/mL); thus, it is conceivable that also in vivo this cytokine may modify the susceptibility of macrophages to HIV and the ability of dextran sulfate and soluble CD4 to inhibit HIV replication. These results suggest that the in vitro study in M-CSF-treated macrophages of promising drugs inhibitors of HIV-CD4 binding could provide further insights into the potential efficacy of these compounds in patients.
在培养的人原代巨噬细胞中，研究了巨噬细胞集落刺激因子（M-CSF）对CD4受体表达、对1型人类免疫缺陷病毒（HIV）感染的易感性以及硫酸葡聚糖和可溶性CD4的抗HIV活性的影响。M-CSF刺激巨噬细胞表达CD4受体，这导致CD4+细胞数量增加以及细胞表面受体密度增加。M-CSF还显著增强了巨噬细胞对HIV感染的易感性。有趣的是，在M-CSF处理的巨噬细胞中，硫酸葡聚糖和可溶性CD4（两种通过不同机制干扰HIV与CD4结合的化合物）的抗HIV活性分别降低了100倍和5倍。据报道，人体血液中M-CSF的浓度与本研究中使用的浓度（1000 U/mL）相似；因此，可以想象在体内这种细胞因子也可能改变巨噬细胞对HIV的易感性以及硫酸葡聚糖和可溶性CD4抑制HIV复制的能力。这些结果表明，在M-CSF处理的巨噬细胞中对有前景的HIV-CD4结合药物抑制剂进行体外研究，可以为这些化合物在患者中的潜在疗效提供进一步的见解。
