CD4(+) T-LYMPHOCYTE MODULATION OF OZONE-INDUCED MURINE PULMONARY INFLAMMATION
CD4(+) T-LYMPHOCYTE MODULATION OF OZONE-INDUCED MURINE PULMONARY INFLAMMATION
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DOI：
10.1165/ajrcmb.12.4.7695918
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发表时间：
1995-04-01
影响因子：
6.4
通讯作者：
WILLSKARP, M
中科院分区：
文献类型：
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作者：
CHEN, XL;GAVETT, SH;WILLSKARP, M
吸入高浓度的臭氧会在肺部产生强烈的炎症反应。小鼠对臭氧暴露的这种反应的程度取决于近交系，C57BL/6J （B6）菌株为敏感表型，C3H/HeJ （C3）菌株为抗性表型。为了研究T淋巴细胞在臭氧诱导的肺部炎症调节中的作用，小鼠通过腹腔注射抗thy1.2单克隆抗体（mAb），抗cd4 (+) mAb或同型匹配的对照抗体（每种0.5 mg）进行预处理，随后暴露于过滤空气或臭氧（0.3 ppm）中72小时。在臭氧暴露后，立即评估支气管肺泡灌洗液（BALF）中的细胞谱。在同型处理的两种小鼠的对照中，臭氧暴露诱导BALF中巨噬细胞、中性粒细胞、淋巴细胞和上皮细胞的数量显著增加；然而，与C3小鼠相比，B6小鼠恢复的每种细胞类型的大小都明显更大。抗thy1.2和抗cd4（+）单克隆抗体均能减少B6小鼠中各类型细胞的恢复数量，增加C3小鼠中各类型细胞的恢复数量。为了确定CD4(+) t细胞来源的细胞因子白细胞介素(IL)-4是否参与了t细胞消耗对C3和B6小鼠臭氧诱导的炎症反应的差异影响，在空气或臭氧暴露前，用400 ng重组小鼠IL-4或载体或5.0 mg抗IL-4受体单克隆抗体或同型匹配抗体预处理小鼠。用抗il -4受体单抗预处理臭氧暴露C3小鼠可显著增加支气管肺泡灌洗（BAL）恢复的细胞数量，但对B6小鼠细胞内流的大小没有影响。IL-4预处理B6小鼠减少了臭氧诱导的细胞内流，但对C3小鼠的细胞内流没有影响。这些结果表明，IL-4抑制臭氧诱导的肺部炎症反应。此外，小鼠菌株对臭氧诱导炎症的敏感性可能部分归因于诱导IL-4产生的遗传差异。
Inhalation of elevated levels of ozone produces a potent inflammatory response in the lung. The magnitude of this response to ozone exposure in mice is inbred strain dependent with the susceptible phenotype being exemplified by the C57BL/6J (B6) strain and the resistant phenotype by the C3H/HeJ (C3) strain. To examine the role of T lymphocytes in the regulation of ozone-induced pulmonary inflammation, mice were pretreated by an intraperitoneal injection of anti-Thy1.2 monoclonal antibody (mAb), anti-CD4(+) mAb, or isotype-matched control antibodies (0.5 mg each) and subsequently exposed for 72 h to either filtered air or ozone (0.3 ppm). Immediately after ozone exposure, the cellular profile in the bronchoalveolar lavage fluids (BALF) was assessed. In isotype-treated controls of both strains of mice, ozone exposure induced significant increases in the numbers of macrophages, neutrophils, lymphocytes, and epithelial cells recovered in the BALF; however, the magnitude of each cell type recovered was significantly greater in B6 mice as compared with C3 mice. Both anti-Thy1.2 and anti-CD4(+) monoclonal antibody treatments decreased the number of each cell type recovered in the B6 mice and increased the number of cells in the C3 mice. To determine if the CD4(+) T-cell-derived cytokine interleukin (IL)-4 was involved in the differential effect of T-cell depletion on the ozone-induced inflammatory responses of C3 and B6 mice, mice were pretreated with either 400 ng of recombinant mouse IL-4 or vehicle, or 5.0 mg anti-IL-4 receptor monoclonal antibody or an isotype-matched antibody before either air or ozone exposure. Pretreatment of ozone-exposed C3 mice with anti-IL-4 receptor mAb significantly increased the numbers of cells recovered by bronchoalveolar lavage (BAL) although it had no effect on the magnitude of the cellular influx in B6 mice. IL-4 pretreatment of the B6 mice reduced the ozone-induced cellular influx although it had no effect on cellular influx in C3 mice. These results suggest that IL-4 inhibits ozone-induced pulmonary inflammatory responses. Moreover, the susceptibility of murine strains to ozone-induced inflammation may be due, in part, to genetic differences in the inducible production of IL-4.