Grinnan Dan, Sung Sun-Sang, Dougherty Joseph A, Knowles Amy Ryce, Allen Matthew B, Rose Charles E, Nakano Hideki, Gunn Michael D, Fu Shu Man, Rose C Edward
Division of Pulmonary and Critical Care Medicine, University of Virginia School of Medicine, Charlottesville, VA 22901, USA.
J Allergy Clin Immunol. 2006 Dec;118(6):1234-41. doi: 10.1016/j.jaci.2006.07.036. Epub 2006 Oct 6.
Dendritic cells and lymphocytes play a central role in allergic asthma. Chemokines for these cells include the CCR7 agonists secondary lymphoid chemokine/CCL21 and EBV-induced lymphoid chemokine/CCL19, but their role in allergic asthma is poorly understood.
We sought to determine the effects of abrogation of lymphoid tissue expression of CCR7 agonists on allergic airway responses.
Paucity of lymphocyte T cell (plt) mutant mice, deficient in EBV-induced lymphoid chemokine/CCL19 and the lymphoid form of secondary lymphoid chemokine/CCL21, were evaluated in an established ovalbumin (OVA)-induced asthma model (plt-OVA group) and compared with similarly immunized +/+ BALB/c mice (+/+OVA group).
APTI responses to methacholine increased similarly in OVA-challenged plt and +/+ mice. However, airway inflammation was strikingly enhanced in plt-OVA mutants over +/+OVA mice and included increased numbers of eosinophils, CD4 and B cells, neutrophils, and total leukocytes in bronchoalveolar lavage fluid and inflammatory cell cuffing around pulmonary arterioles. Enhanced airway inflammation was accompanied by an increase in lung T(H)2 activity, with increased levels of IL-4 and monocyte-derived chemoattractant/CCL22.
Induction of allergic asthma in mutant mice with impaired CCR7 responses results in characteristics that resemble severe asthma in human subjects, including severe bronchial lymphocytosis, eosinophilia, and neutrophilia, but not in enhancement in airway hyperreactivity.
Disruption of chemokines responsible for trafficking of antigen-processing cells and lymphocytes to the draining lymph nodes might lead to enhanced allergic airway responses.
树突状细胞和淋巴细胞在过敏性哮喘中起核心作用。这些细胞的趋化因子包括CCR7激动剂二级淋巴趋化因子/CCL21和EB病毒诱导的淋巴趋化因子/CCL19，但它们在过敏性哮喘中的作用尚不清楚。
我们试图确定CCR7激动剂的淋巴组织表达缺失对过敏性气道反应的影响。
在已建立的卵清蛋白（OVA）诱导的哮喘模型中评估缺乏EB病毒诱导的淋巴趋化因子/CCL19和二级淋巴趋化因子/CCL21淋巴形式的淋巴细胞T细胞（plt）突变小鼠（plt-OVA组），并与同样免疫的+/ + BALB/c小鼠（+/ + OVA组）进行比较。
在OVA激发的plt小鼠和+/ +小鼠中，对乙酰甲胆碱的气道反应性增加相似。然而，与+/ + OVA小鼠相比，plt-OVA突变体中的气道炎症明显增强，包括支气管肺泡灌洗液中嗜酸性粒细胞、CD4和B细胞、中性粒细胞和总白细胞数量增加，以及肺小动脉周围的炎症细胞套袖。气道炎症增强伴随着肺T(H)2活性增加，IL-4和单核细胞衍生的趋化因子/CCL22水平升高。
CCR7反应受损的突变小鼠中诱导过敏性哮喘会导致类似于人类严重哮喘的特征，包括严重的支气管淋巴细胞增多、嗜酸性粒细胞增多和中性粒细胞增多，但气道高反应性没有增强。
负责将抗原处理细胞和淋巴细胞运输到引流淋巴结的趋化因子的破坏可能导致过敏性气道反应增强。
