Zembala M, Pryjma J, Plucienniczak A, Szczepanek A, Jasinski M, Ruggiero I, Piselli P, Colizzi V
Department of Clinical Immunology, Polish-American Institute of Pediatrics, Jagiellonian University Medical College, Cracow.
Clin Immunol Immunopathol. 1995 May;75(2):131-9. doi: 10.1006/clin.1995.1062.
The HIV-1 gp120 recombinant protein fragment encompassing aa residues 410-511, that contains the CD4 binding region (rp120cd), and fragment aa 446-511, which lacks the sequence responsible for CD4 binding (rp120), were synthesized to study their ability to induce TNF synthesis in human monocytes. The rp120cd stimulated TNF alpha secretion by monocytes while the rp120 and full-length recombinant protein (FL gp120), used as control, failed to do so. However, FL gp120 stimulated peripheral blood mononuclear cells (PBMC) and lymphocytes for TNF production and this was inhibited by anti-CD4 MAb. The rp120cd also caused TNF secretion by PBMC that was not blocked by this antibody. Furthermore, FL gp120 but not rp120cd inhibited anti-CD4 mAb binding to CEM cells. Hence, FL gp120 may cause TNF release from lymphocytes by binding to CD4, while rp120cd interacts with monocytes but not lymphocytes and induces TNF production by a mechanism not involving CD4 binding. Unexpectedly, FL gp120 but not rp120cd stimulated IL-6 secretion and IL-6 mRNA synthesis in monocytes. The FL gp120-induced production of IL-6 by monocytes was inhibited by anti-CD4 monoclonal antibody (MAb). Thus, there may be different requirements for TNF induction in lymphocytes and monocytes stimulated with various preparations of gp120 and for the selective induction of cytokines in monocytes. The enhanced production of TNF in HIV infection and AIDS may involve distinct cellular sources and different mechanisms.
合成了包含410 - 511位氨基酸残基、含有CD4结合区域的HIV-1 gp120重组蛋白片段（rp120cd）以及缺少负责CD4结合序列的446 - 511位氨基酸片段（rp120），以研究它们在人单核细胞中诱导肿瘤坏死因子（TNF）合成的能力。rp120cd刺激单核细胞分泌TNFα，而作为对照的rp120和全长重组蛋白（FL gp120）则未能如此。然而，FL gp120刺激外周血单核细胞（PBMC）和淋巴细胞产生TNF，且这一过程被抗CD4单克隆抗体（MAb）抑制。rp120cd也能使PBMC分泌TNF，而该抗体不能阻断这一过程。此外，FL gp120而非rp120cd抑制抗CD4 mAb与CEM细胞的结合。因此，FL gp120可能通过与CD4结合导致淋巴细胞释放TNF，而rp120cd与单核细胞而非淋巴细胞相互作用，并通过不涉及CD4结合的机制诱导TNF产生。出乎意料的是，FL gp120而非rp120cd刺激单核细胞分泌白细胞介素-6（IL-6）并合成IL-6 mRNA。FL gp120诱导单核细胞产生IL-6的过程被抗CD4单克隆抗体（MAb）抑制。因此，在用各种gp120制剂刺激时，淋巴细胞和单核细胞中TNF诱导可能存在不同要求，且单核细胞中细胞因子的选择性诱导也可能不同。HIV感染和艾滋病中TNF产生的增加可能涉及不同的细胞来源和不同机制。
