Dextran sulfate and heparin interact with CD4 molecules to inhibit the binding of coat protein (gp120) of HIV.
Dextran sulfate and heparin interact with CD4 molecules to inhibit the binding of coat protein (gp120) of HIV.
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DOI：
10.4049/jimmunol.143.4.1149
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发表时间：
1989-08
影响因子：
4.4
通讯作者：
Seth Lederman;Roy M. Gulick;Leonard Chess
中科院分区：
文献类型：
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作者：
Seth Lederman;Roy M. Gulick;Leonard Chess
硫酸葡聚糖、肝素和某些其他硫酸化多糖可有效抑制 HIV 对 CD4+ 细胞的吸附。这种抑制的机制尚不清楚，具体来说，尚不清楚这些药物是否在 CD4-gp120 结合水平上起作用。例如，之前的报告表明，硫酸葡聚糖不会抑制已知针对 gp120 结合位点的抗 CD4 mAb 的细胞表面结合。为了证实和扩展这些观察结果，在本研究中，通过细胞荧光法测量，硫酸葡聚糖不抑制 OKT4A、OKT4C、Leu3a 或 B66.6 与 CD4+ 细胞的结合。接下来，利用重组形式的 CD4 (rT4) 和 gp120 (rgp120) 在没有其他病毒或细胞结构的情况下直接研究它们的分子相互作用。开发了相互固相 ELISA 测定法来直接研究硫酸化多糖对 rT4 与固定化 rgp120 结合的影响，反之亦然。硫酸葡聚糖、肝素和岩藻依聚糖（但不包括硫酸软骨素）抑制 rgp120 与 rT4 的结合。重要的是，固定化rT4而非固定化rgp120的硫酸葡聚糖和肝素预处理抑制了rT4-rgp120结合。总而言之，这些数据表明，虽然硫酸多糖和抗 CD4 mAb 均抑制 gp120 结合，但硫酸多糖与 CD4 上与抗体结合的位点不同的位点相互作用。
Dextran sulfate, heparin, and certain other sulfated polysaccharides potently inhibit the adsorption of HIV to CD4+ cells. The mechanism of this inhibition is unclear and, specifically, it is unknown if these agents act at the level of CD4-gp120 binding. For example, previous reports have demonstrated that dextran sulfate does not inhibit the cell surface binding of anti-CD4 mAb known to be directed at the gp120 binding site. In order to confirm and extend these observations, in the present study, it was shown that dextran sulfate does not inhibit the binding of OKT4A, OKT4C, Leu3a, or B66.6 to CD4+ cells as measured by cytofluorography. Next, recombinant forms of CD4 (rT4) and gp120 (rgp120) were utilized to directly study their molecular interaction in the absence of other viral or cellular structures. Reciprocal solid phase ELISA assays were developed to study directly the effects of sulfated polysaccharides on the binding of rT4 to immobilized rgp120 and vice versa. Dextran sulfate, heparin, and fucoidan, but not chondroitin sulfate, inhibited the binding of rgp120 to rT4. Importantly, dextran sulfate and heparin pre-treatment of immobilized rT4, but not immobilized rgp120, inhibited rT4-rgp120 binding. Taken together, these data suggest that while both sulfated polysaccharides and anti-CD4 mAb inhibit gp120 binding, the sulfated polysaccharides interact with sites on CD4 that are distinct from those with which the antibodies bind.