Nakashima Adriane S, Prado Carla M, Lanças Tatiana, Ruiz Viviane C, Kasahara David I, Leick-Maldonado Edna A, Dolhnikoff Marisa, Martins Milton A, Tibério Iolanda F L C
Departamento de Clínica Médica, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, São Paulo SP, Brazil.
J Appl Physiol (1985). 2008 Jun;104(6):1778-85. doi: 10.1152/japplphysiol.00830.2007. Epub 2008 Apr 3.
Recent studies emphasize the presence of alveolar tissue inflammation in asthma. Immunotherapy has been considered a possible therapeutic strategy for asthma, and its effect on lung tissue had not been previously investigated. Measurements of lung tissue resistance and elastance were obtained before and after both ovalbumin and acetylcholine challenges. Using morphometry, we assessed eosinophil and smooth muscle cell density, as well as collagen and elastic fiber content, in lung tissue from guinea pigs with chronic pulmonary allergic inflammation. Animals received seven inhalations of ovalbumin (1-5 mg/ml; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). The ovalbumin-exposed animals presented an increase in baseline and in postchallenge resistance and elastance related to baseline, eosinophil density, and collagen and elastic fiber content in lung tissue compared with controls. Baseline and post-ovalbumin and acetylcholine elastance and resistance, eosinophil density, and collagen and elastic fiber content were attenuated in OT1 and OT2 groups compared with the OVA group. Our results show that inducing oral tolerance attenuates lung tissue mechanics, as well as eosinophilic inflammation and extracellular matrix remodeling induced by chronic inflammation.
近期研究强调了哮喘中肺泡组织炎症的存在。免疫疗法已被视为哮喘的一种可能治疗策略,但其对肺组织的影响此前尚未得到研究。在卵清蛋白和乙酰胆碱激发前后均测量了肺组织阻力和弹性。我们使用形态计量学评估了患有慢性肺部过敏性炎症的豚鼠肺组织中的嗜酸性粒细胞和平滑肌细胞密度,以及胶原蛋白和弹性纤维含量。动物在4周内接受了7次卵清蛋白(1 - 5毫克/毫升;OVA组)或生理盐水(SAL组)吸入。从第1次吸入(OT1组)或第4次吸入后(OT2组)开始,通过在无菌饮用水中随意提供2%的卵清蛋白来诱导口服耐受。与对照组相比,暴露于卵清蛋白的动物在基线以及激发后与基线相关的阻力和弹性、嗜酸性粒细胞密度以及肺组织中的胶原蛋白和弹性纤维含量均增加。与OVA组相比,OT1组和OT2组的基线以及卵清蛋白和乙酰胆碱激发后的弹性和阻力、嗜酸性粒细胞密度以及胶原蛋白和弹性纤维含量均降低。我们的结果表明,诱导口服耐受可减轻肺组织力学以及慢性炎症诱导的嗜酸性粒细胞炎症和细胞外基质重塑。