Immunostimulatory oligonucleotides attenuate airways remodeling in allergic monkeys

Immunostimulatory oligonucleotides attenuate airways remodeling in allergic monkeys
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DOI:
10.1164/rccm.200404-533oc
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发表时间:
2004-12-01
影响因子:
24.7
通讯作者:
Miller, LA
Miller, LA
中科院分区:
医学1区
文献类型:
--
作者:
Fanucchi, MV;Schelegle, ES;Miller, LA

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为确定吸入含CpG基序的免疫刺激DNA序列寡核苷酸是否能减轻哮喘表型(气道高反应性和气道重塑)的病理生理表现,对实验性过敏性呼吸道疾病的恒河猴进行了7次免疫刺激寡核苷酸(或假手术)治疗,共33周。免疫刺激DNA序列处理的猴子与假处理的猴子相比,呼吸道高反应性降低了两倍。免疫刺激寡核苷酸处理的猴子的呼吸道有更薄的网状基底膜,更少的粘液细胞,更少的嗜酸性粒细胞,以及更少的肥大细胞。我们的结论是,吸入免疫刺激寡核苷酸可以减轻实验诱导的过敏性呼吸道疾病的非人灵长类动物的气道高反应性和气道重塑的程度。
To determine whether inhaled immunostimulatory DNA sequence oligonucleotides containing CpG motifs mitigate the pathophysiologic manifestation of the asthmatic phenotype (airways hyperresponsiveness and airways remodeling), rhesus monkeys with experimentally induced allergic airways disease were treated seven times with inhaled immunostimulatory oligonucleotides (or sham) periodically for 33 weeks. Airways hyperresponsiveness was reduced twofold in immunostimulatory DNA sequence-treated compared with sham-treated monkeys. Airways from immunostimulatory oligonucleotide-treated monkeys had thinner reticular basement membranes, fewer mucous cells, fewer eosinophils, and fewer mast cells than sham-treated allergic monkeys. We conclude that inhaled immunostimulatory oligonucleotides can attenuate the magnitude of airway hyperreactivity and airways remodeling produced in nonhuman primates with experimentally induced allergic airways disease.