Edwan Jehad H, Perry Greg, Talmadge James E, Agrawal Devendra K
Department of Medical Microbiology and Immunology, and Center for Allergy, Asthma, and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
J Immunol. 2004 Apr 15;172(8):5016-23. doi: 10.4049/jimmunol.172.8.5016.
Flt3 ligand (Flt3-L) is a growth factor for dendritic cells and induces type 1 T cell responses. We recently reported that Flt3-L prevented OVA-induced allergic airway inflammation and suppressed late allergic response and airway hyper-responsiveness (AHR). In the present study we examined whether Flt3-L reversed allergic airway inflammation in an established model of asthma. BALB/c mice were sensitized and challenged with OVA, and AHR to methacholine was established. Then mice with AHR were randomized and treated with PBS or 6 microg of Flt3-L i.p. for 10 days. Pulmonary functions and AHR to methacholine were examined after rechallenge with OVA. Treatment with Flt3-L of presensitized mice significantly suppressed (p < 0.001) the late allergic response, AHR, bronchoalveolar lavage fluid total cellularity, absolute eosinophil counts, and inflammation in the lung tissue. There was a significant decrease in proinflammatory cytokines (TNF-alpha, IL-4, and IL-5) in bronchoalveolar lavage fluid, with a significant increase in serum IL-12 and a decrease in serum IL-5 levels. There was no significant effect of Flt3-L treatment on serum IL-4 and serum total IgE levels. Sensitization with OVA significantly increased CD11b(+)CD11c(+) cells in the lung, and this phenomenon was not significantly affected by Flt3-L treatment. These data suggest that Flt3-L can reverse allergic airway inflammation and associated changes in pulmonary functions in murine asthma model.
Flt3配体（Flt3-L）是一种树突状细胞生长因子，可诱导1型T细胞反应。我们最近报道，Flt3-L可预防卵清蛋白（OVA）诱导的过敏性气道炎症，并抑制迟发性过敏反应和气道高反应性（AHR）。在本研究中，我们检测了Flt3-L是否能逆转已建立的哮喘模型中的过敏性气道炎症。用OVA对BALB/c小鼠进行致敏和激发，建立对乙酰甲胆碱的AHR。然后将有AHR的小鼠随机分组，腹腔注射PBS或6μg Flt3-L，持续10天。用OVA再次激发后检测肺功能和对乙酰甲胆碱的AHR。用Flt3-L治疗预先致敏的小鼠可显著抑制（p<0.001）迟发性过敏反应、AHR、支气管肺泡灌洗液总细胞数、绝对嗜酸性粒细胞计数以及肺组织炎症。支气管肺泡灌洗液中促炎细胞因子（TNF-α、IL-4和IL-5）显著减少，血清IL-12显著增加，血清IL-5水平降低。Flt3-L治疗对血清IL-4和血清总IgE水平无显著影响。用OVA致敏可显著增加肺中CD11b(+)CD11c(+)细胞，这种现象不受Flt3-L治疗的显著影响。这些数据表明，Flt3-L可逆转小鼠哮喘模型中的过敏性气道炎症及相关的肺功能变化。
