Murali R, Wolfe J H, Erber R, Chice S M, Murali M R, Durkin H G, Zach P, Auci D L
Department of Pathology, State University of New York Health Science Center at Brooklyn, NY 11203, USA.
J Leukoc Biol. 1998 Aug;64(2):198-202. doi: 10.1002/jlb.64.2.198.
Urokinase (UK) type plasminogen activator is a serine protease produced by activated human monocytes. Despite the well-documented roles played by UK in cell-mediated immunity in healthy humans, the roles played by UK in the derangements of cell-mediated immune responses observed in HIV disease remain largely undefined. In these studies the numbers of peripheral blood lymphocytes and monocytes bearing surface UK (UK+) as well as serum levels of UK (flow microfluorimetry and ELISA, respectively) were determined in children with AIDS and in healthy HIV-negative children. The effects of exogenous UK on lymphocyte activation (cell cycle analysis using living cells) and surface marker (CD3, CD4, CD8, and CD19) expression (flow microfluorimetry using fixed cells) were also studied. Data are expressed as percent total cells. Numbers of UK+ lymphocytes in children with AIDS were similar to those observed in healthy children. In contrast, numbers of UK+ peripheral blood monocytes were dramatically decreased (> 70%) in the children with AIDS. However, serum levels of UK were increased (nearly threefold) in these children. When lymphocytes from these children were cultured with soluble UK, numbers of cells in S phase of cell cycle appeared suppressed. Incubation of fixed lymphocytes from either a child with AIDS or from a healthy child with exogenous UK appeared to increase numbers of cells expressing CD3. Incubation with UK had no effect on expression of any other surface marker (CD4, CD8, or CD19) using cells from the child with AIDS. In contrast, incubation with UK appeared to decrease (fivefold) numbers of cells expressing CD19 and increase numbers of cells expressing CD4 and CD8 only when fixed lymphocytes from a healthy HIV-negative child were used. The results suggest important roles for UK in regulation of lymphocyte surface markers in general and in CD3- and CD19-dependent lymphocyte activation pathways specifically. Furthermore, these studies add to a widening body of evidence implicating UK dysregulation in the pathogenesis of HIV disease and may point to pharmacological opportunities involving UK to delay or prevent progression of HIV infection into full-blown AIDS.
尿激酶（UK）型纤溶酶原激活剂是一种由活化的人类单核细胞产生的丝氨酸蛋白酶。尽管UK在健康人体内细胞介导的免疫中所起的作用已有充分记载，但UK在HIV疾病中观察到的细胞介导免疫反应紊乱中所起的作用仍基本不明。在这些研究中，测定了艾滋病患儿和健康的HIV阴性儿童外周血中携带表面UK（UK+）的淋巴细胞和单核细胞数量以及UK的血清水平（分别采用流式微荧光法和酶联免疫吸附测定法）。还研究了外源性UK对淋巴细胞活化（使用活细胞进行细胞周期分析）和表面标志物（CD3、CD4、CD8和CD19）表达（使用固定细胞进行流式微荧光法）的影响。数据以占总细胞的百分比表示。艾滋病患儿中UK+淋巴细胞的数量与健康儿童中观察到的相似。相比之下，艾滋病患儿中UK+外周血单核细胞的数量显著减少（超过70%）。然而，这些患儿的UK血清水平升高（近三倍）。当用可溶性UK培养这些患儿的淋巴细胞时，细胞周期S期的细胞数量似乎受到抑制。用外源性UK孵育艾滋病患儿或健康儿童的固定淋巴细胞，似乎会增加表达CD3的细胞数量。使用艾滋病患儿的细胞时，用UK孵育对任何其他表面标志物（CD4、CD8或CD19）的表达均无影响。相比之下，仅当使用健康的HIV阴性儿童的固定淋巴细胞时，用UK孵育似乎会使表达CD19的细胞数量减少（五倍），并增加表达CD4和CD8的细胞数量。结果表明，UK总体上在淋巴细胞表面标志物的调节中，特别是在CD3和CD19依赖性淋巴细胞活化途径中发挥重要作用。此外，这些研究增加了越来越多的证据，表明UK失调与HIV疾病的发病机制有关，并可能指出涉及UK的药理学机会，以延缓或预防HIV感染发展为全面的艾滋病。
