Dose-Dependent Activation of Lymphocytes in Endotoxin-Induced Airway Inflammation
Dose-Dependent Activation of Lymphocytes in Endotoxin-Induced Airway Inflammation
复制标题
内毒素诱导的气道炎症中淋巴细胞的剂量依赖性激活
作者：
R. Larsson;David Rocksén;B. Lilliehöök;Åsa Jonsson;A. Bucht
摘要吸入内毒素后，中性粒细胞重新聚集到肺组织和空气中是炎症事件的一个标志。我们研究了不同的淋巴细胞亚群在这种炎症中的作用，这种炎症被认为主要涉及先天性免疫系统。雾化吸入大肠杆菌可引起小鼠支气管肺泡灌洗液中中性粒细胞数呈剂量依赖性增加，低剂量组12h达最大值，高剂量组24h达最大值。肺组织基因表达谱显示，低剂量的内毒素可使促炎细胞因子和趋化因子提前(2 H)和短暂地出现，而大剂量的内毒素可引起更多的延迟和持续的激活(6~12 h)。低剂量的干扰素、白介素2(IL-2)、RANTES和IL-2受体的α链不表达，而高剂量的脂多糖诱导这些基因的强烈表达，表明T细胞的激活具有剂量依赖性。IL-17也观察到了类似的模式，支持只有在高剂量的内毒素暴露时T细胞对中性粒细胞炎症的贡献。使用定义淋巴细胞亚群功能缺陷的小鼠，进一步研究了淋巴细胞在炎症反应中的作用。γδT细胞和B细胞缺陷小鼠的反应与相应的野生型小鼠相似。通过体内注射pk136抗体选择性地消耗NK细胞并不显著影响中性粒细胞在空气中的募集。因此，无论是NK细胞、B细胞还是γδT细胞都不参与宿主的反应，提示在淋巴细胞亚群中，αβT细胞仅参与内毒素诱导的呼吸道炎症。
ABSTRACT Recruitment of neutrophils to lung tissue and airspaces is a hallmark of inflammatory events following inhalation of endotoxins. We studied the role of different lymphocyte subsets in this inflammation, which is assumed to primarily involve the innate immune system. Inhalation of aerosolized Escherichia colilipopolysaccharide (LPS) in mice induced a dose-dependent increase in neutrophils in bronchoalveolar lavage fluid, reaching a maximum after 12 h at a low dose and after 24 h at a high dose. Profiles of gene expression in lung tissue indicated an early (2 h) and transient onset of proinflammatory cytokines and chemokines by a low dose of LPS, while a high dose caused more delayed and sustained (6 to 12 h) activation. Gamma interferon, interleukin-2 (IL-2), RANTES, and the α chain of the IL-2 receptor were not expressed at a low dose, whereas a high dose of LPS induced a strong expression of these genes, indicating a dose-dependent activation of T cells. A similar pattern was observed for IL-17, supporting a contribution of T cells to the neutrophilic inflammation only at high-dose exposure to LPS. The involvement of lymphocytes in the inflammatory response was further studied using mice with functional deficiencies in defined lymphocyte subsets. Both γδ T-cell- and B-cell-deficient mice displayed a response similar to that of the corresponding wild-type strains. Selective depletion of NK cells by in vivo administration of the pk136 antibody did not significantly affect the recruitment of neutrophils into airspaces. Thus, neither NK cells, B cells, nor γδ T cells appeared to participate in the host response, suggesting that among the lymphocyte subsets, αβ T cells are exclusively involved in endotoxin-induced airway inflammation.
影响因子：
4.4
作者：
Hagen Schmal;T. Shanley;M. Jones;H. Friedl;P. Ward
通讯作者：
Hagen Schmal;T. Shanley;M. Jones;H. Friedl;P. Ward
IL-1 和 IL-1 受体拮抗剂。
DOI：
--
发表时间：
1995
期刊：
Nutrition (Burbank, Los Angeles County, Calif.)
影响因子：
--
作者：
Dinarello,CA
通讯作者：
Dinarello,CA
CD4 T 淋巴细胞耗竭减弱了小鼠肺泡巨噬细胞脂多糖诱导的肿瘤坏死因子分泌。
DOI：
--
发表时间：
1994
期刊：
Lymphokine and cytokine research
影响因子：
--
作者：
D'Souza,NB;Mandujano,FJ;Nelson,S;Summer,WR;Shellito,JE
通讯作者：
Shellito,JE