Dziedzic D, White H J
Environ Res. 1986 Dec;41(2):610-22. doi: 10.1016/s0013-9351(86)80155-4.
As part of a project to assess the effect of ozone inhalation on cells of the mediastinal lymph nodes, groups of CD-1 female mice were exposed to ozone at 0.3, 0.5, and 0.7 ppm, 20 hr per day, 7 days per week for 1-28 days. The effect of ozone exposure on lymphoid cells was determined by studying mediastinal lymph nodes at various times of exposure. We found that lymphocyte numbers underwent a dose-dependent, four-phased change: cellular depletion (Days 1-2), followed by rapid hyperplasia (Days 3-4), incremental cell number reduction (Days 5-7), and a subsequent subacute phase of elevated lymphocyte numbers (Days 8-28). Using tritiated thymidine we determined that cells underwent a rapid burst of division by Day 3 of exposure and that mitosis subsequently declined to near baseline values by 2 weeks of exposure. Autoradiographic analysis of histologic sections revealed that the paracortical T-cell areas of the nodes were particularly involved. In addition to the increase in thymidine uptake, several morphologic changes were evident in affected cells including cellular reorganization, nuclear and cellular hypertrophy, and induction of a prominent nucleolus. By comparison, the B cells from ozone-exposed animals were virtually unaffected with respect to cell division or morphological alterations. Prior treatment of ozone-exposed animals with a monoclonal antibody that is cytotoxic for T cells eliminated the hyperplastic response. Since T cells seemed particularly affected by ozone inhalation, we studied immunologic aspects of T-cell reactivity. T-cell responsiveness to mitogenic stimulation with concanavalin A showed little alteration during the first days of exposure; however, by Day 14 an increase in reactivity was observed. This change indicated that functional lymphocyte stimulation occurred during ozone exposure. Thus, response to ozone inhalation involves an acute phase (Days 1-7) characterized by a hyperplastic increase in cell mass and a subacute phase (Days 8-28) characterized by functional changes in lymphocyte reactivity.
作为评估吸入臭氧对纵隔淋巴结细胞影响的项目的一部分，将几组CD-1雌性小鼠每天20小时、每周7天暴露于浓度为0.3、0.5和0.7 ppm的臭氧中，持续1 - 28天。通过在不同暴露时间研究纵隔淋巴结来确定臭氧暴露对淋巴细胞的影响。我们发现淋巴细胞数量呈现剂量依赖性的四阶段变化：细胞耗竭期（第1 - 2天），随后是快速增生期（第3 - 4天），细胞数量逐渐减少期（第5 - 7天），以及随后淋巴细胞数量升高的亚急性期（第8 - 28天）。使用氚标记的胸腺嘧啶核苷，我们确定细胞在暴露第3天时经历了快速的分裂爆发，随后到暴露2周时有丝分裂降至接近基线值。组织学切片的放射自显影分析显示，淋巴结的副皮质T细胞区尤其受到影响。除了胸腺嘧啶核苷摄取增加外，受影响的细胞还出现了几种形态学变化，包括细胞重组、细胞核和细胞肥大以及显著核仁的诱导。相比之下，暴露于臭氧的动物的B细胞在细胞分裂或形态改变方面几乎未受影响。用对T细胞具有细胞毒性的单克隆抗体预先处理暴露于臭氧的动物，消除了增生反应。由于T细胞似乎特别受吸入臭氧的影响，我们研究了T细胞反应性的免疫学方面。T细胞对伴刀豆球蛋白A促有丝分裂刺激的反应性在暴露的最初几天几乎没有变化；然而，到第14天时观察到反应性增加。这一变化表明在臭氧暴露期间发生了功能性淋巴细胞刺激。因此，对吸入臭氧的反应包括一个以细胞质量增生性增加为特征的急性期（第1 - 7天）和一个以淋巴细胞反应性功能变化为特征的亚急性期（第8 - 28天）。
