The LD78β isoform of MIP-1α is the most potent CCR5 agonist and HIV-1-inhibiting chemokine
The LD78β isoform of MIP-1α is the most potent CCR5 agonist and HIV-1-inhibiting chemokine
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DOI：
10.1172/jci7318
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发表时间：
1999-08-01
影响因子：
15.9
通讯作者：
Van Damme, J
中科院分区：
文献类型：
--
作者：
Menten, P;Struyf, S;Van Damme, J
LD 78 α和LD 78 β是2个高度相关的非等位基因，编码人CC趋化因子巨噬细胞炎性蛋白-1 α（MIP-1 α）的不同亚型。从刺激的外周血单核细胞的条件培养基中鉴定出两种分子形式的天然LD 78 β（7.778和7.793 kDa）。虽然LD 78 α和LD 78 β仅在3个氨基酸上不同，但两种LD 78 β变体对小鼠淋巴细胞的化学引诱剂比LD 78 α强100倍。相反，LD 78 β在化学吸引人淋巴细胞和单核细胞方面仅比LD 78 α有效2倍。使用CC趋化因子受体转染的细胞，LD 78 β的两种分子形式证明在通过CCR 5诱导细胞内钙升高方面比LD 78 α有效得多。与LD 78 α和RANTES相比，LD 78 β与CCR 5的这种优先结合导致了10- 50倍更高的抑制使用CCR 5的（R5）HIV-1菌株感染外周血单核细胞的效力。迄今为止，LD 78 β是抑制HIV-1感染的最有效的趋化因子，并且可以被认为是治疗R5 HIV-1毒株感染的潜在重要候选药物。
LD78 alpha and LD78 beta are 2 highly related nonallelic genes that code for different isoforms of the human CC chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha). Two molecular forms of natural LD78 beta (7.778 and 7.793 kDa) were identified from conditioned media of stimulated peripheral blood mononuclear cells. Although LD78 alpha and LD78 beta only differ in 3 amino acids, both LD78 beta variants were 100-fold more potent chemoattractants for mouse lymphocytes than was LD78 alpha. On the contrary, LD78 beta was only 2-fold more efficient than LD78 alpha in chemoattracting human lymphocytes and monocytes. Using CC chemokine receptor-transfected cells, both molecular forms of LD78 beta proved to be much more potent than LD78 alpha in inducing an intracellular calcium rise through CCR5. Compared with LD78 alpha and RANTES, this preferential binding of LD78 beta to CCR5 resulted in a 10- to 50-fold higher potency in inhibiting infection of peripheral blood mononuclear cells by CCR5-using (R5) HIV-1 strains. To date, LD78 beta is the most potent chemokine for inhibiting HIV-1 infection, and can be considered as a potentially important drug candidate for the treatment of infection with R5 HIV-1 strains.