Fanucchi Michelle V, Schelegle Edward S, Baker Gregory L, Evans Michael J, McDonald Ruth J, Gershwin Laurel J, Raz Eyal, Hyde Dallas M, Plopper Charles G, Miller Lisa A
Department of Anatomy, Physiology and Cell Biology, University of California, School of Veterinary Medicine, One Shields Avenue, Davis, CA 95616, USA.
Am J Respir Crit Care Med. 2004 Dec 1;170(11):1153-7. doi: 10.1164/rccm.200404-533OC. Epub 2004 Aug 11.
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.
为了确定含有CpG基序的吸入性免疫刺激DNA序列寡核苷酸是否能减轻哮喘表型的病理生理表现(气道高反应性和气道重塑),对实验性诱导过敏性气道疾病的恒河猴进行了33周的周期性吸入免疫刺激寡核苷酸(或假处理)治疗,共7次。与假处理的猴子相比,接受免疫刺激DNA序列治疗的猴子气道高反应性降低了两倍。与假处理的过敏性猴子相比,接受免疫刺激寡核苷酸治疗的猴子的气道网状基底膜更薄,黏液细胞更少,嗜酸性粒细胞更少,肥大细胞也更少。我们得出结论,吸入性免疫刺激寡核苷酸可以减轻实验性诱导过敏性气道疾病的非人类灵长类动物产生的气道高反应性和气道重塑程度。