Ruth J H, Lukacs N W, Warmington K S, Polak T J, Burdick M, Kunkel S L, Strieter R M, Chensue S W
Department of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Ann Arbor, MI 48105, USA.
J Immunol. 1998 Oct 15;161(8):4276-82.
Eotaxin participation was analyzed during types 1 and 2 lung granuloma formation induced by embolizing Sepharose beads coupled to purified protein derivative (PPD) of Mycobacterium bovis or soluble Ags derived from Schistosoma mansoni eggs. Eotaxin was monitored by protein ELISA and semiquantitative reverse-transcriptase PCR mRNA analysis. Both types 1 and 2 granulomas released eotaxin, but levels were sixfold greater (on day 4) in the type 2 than for the type 1 or foreign body granulomas. Transcripts for eotaxin, IL-4, and CCR3 (eotaxin receptor) were also enhanced during type 2 granuloma formation. Anti-IL-4 treatment impaired eotaxin mRNA in lungs with type 2 granulomas, indicating that IL-4 promoted local eotaxin expression. In vivo, anti-eotaxin treatment caused modest reductions in the size of both types 1 and 2 lesions, with negligible effect on eosinophil recruitment. Surprisingly, anti-eotaxin treatment abrogated IFN-gamma-producing cells in regional lymph nodes during the type 1 PPD response. Lymph nodes draining both types 1 and 2 lesions showed enhanced CCR3 mRNA, but this followed the time of maximum eotaxin protein and mRNA expression. Correlative, in vitro studies revealed that graded doses of eotaxin increased IFN-gamma production from PPD-sensitive regional lymph node cultures, while monocyte-chemotactic protein-1, an important macrophage chemoattractant, had the opposite effect. These findings indicate that eotaxin expression is not limited to type 2 hypersensitivity granulomas, but also promotes IFN-gamma production during mycobacterial responses.
在由偶联牛分枝杆菌纯化蛋白衍生物（PPD）的琼脂糖珠或曼氏血吸虫卵衍生的可溶性抗原栓塞诱导的1型和2型肺肉芽肿形成过程中，分析了嗜酸性粒细胞趋化因子的参与情况。通过蛋白质ELISA和半定量逆转录酶PCR mRNA分析监测嗜酸性粒细胞趋化因子。1型和2型肉芽肿均释放嗜酸性粒细胞趋化因子，但2型肉芽肿中嗜酸性粒细胞趋化因子水平（在第4天）比1型或异物肉芽肿高6倍。在2型肉芽肿形成过程中，嗜酸性粒细胞趋化因子、白细胞介素-4和CCR3（嗜酸性粒细胞趋化因子受体）的转录物也有所增强。抗白细胞介素-4治疗损害了2型肉芽肿肺组织中嗜酸性粒细胞趋化因子mRNA的表达，表明白细胞介素-4促进了局部嗜酸性粒细胞趋化因子的表达。在体内，抗嗜酸性粒细胞趋化因子治疗使1型和2型病变的大小适度减小，对嗜酸性粒细胞募集的影响可忽略不计。令人惊讶的是，抗嗜酸性粒细胞趋化因子治疗在1型PPD反应期间消除了局部淋巴结中产生干扰素-γ的细胞。引流1型和2型病变的淋巴结显示CCR3 mRNA增强，但这发生在嗜酸性粒细胞趋化因子蛋白和mRNA表达的高峰期之后。相关的体外研究表明，不同剂量的嗜酸性粒细胞趋化因子可增加PPD敏感局部淋巴结培养物中干扰素-γ的产生，而单核细胞趋化蛋白-1（一种重要的巨噬细胞趋化剂）则有相反的作用。这些发现表明，嗜酸性粒细胞趋化因子的表达不仅限于2型超敏反应性肉芽肿，而且在分枝杆菌反应期间也促进干扰素-γ的产生。
