Montefort S, Gratziou C, Goulding D, Polosa R, Haskard D O, Howarth P H, Holgate S T, Carroll M P
Department of Immunopharmacology, University Medicine, Southampton General Hospital, United Kingdom.
J Clin Invest. 1994 Apr;93(4):1411-21. doi: 10.1172/JCI117118.
We have examined the mucosal changes occurring in bronchial biopsies from six atopic asthmatics 5-6 h after local endobronchial allergen challenge and compared them with biopsies from saline-challenged segments from the same subjects at the same time point. All the subjects developed localized bronchoconstriction in the allergen-challenged segment and had a decrease in forced expiratory volume in 1 s (FEV1) (P < 0.01) and a decrease in their methacholine provocative concentration of agonist required to reduce FEV1 from baseline by 20% (P < 0.05) 24 h postchallenge. At 6 h we observed an increase in neutrophils (P = 0.03), eosinophils (P = 0.025), mast cells (P = 0.03), and CD3+ lymphocytes (P = 0.025), but not in CD4+ or CD8+ lymphocyte counts. We also detected an increase in endothelial intercellular adhesion molecule type 1 (P < 0.05) and E-selectin (P < 0.005), but not vascular cell adhesion molecule type 1 expression with a correlative increase in submucosal and epithelial LFA+ leucocytes (P < 0.01). Thus, in sensitized asthmatics, local endobronchial allergen instillation leads to an increased inflammatory cell infiltrate of the airway mucosa that involves upregulation of specific adhesion molecules expressed on the microvasculature.
我们检查了6名特应性哮喘患者在支气管内局部过敏原激发后5 - 6小时支气管活检组织中发生的黏膜变化,并将其与同一受试者在同一时间点用生理盐水激发的节段的活检组织进行比较。所有受试者在过敏原激发节段均出现局部支气管收缩,且在激发后24小时,1秒用力呼气量(FEV1)下降(P < 0.01),使FEV1从基线降低20%所需的乙酰甲胆碱激发浓度降低(P < 0.05)。在6小时时,我们观察到中性粒细胞(P = 0.03)、嗜酸性粒细胞(P = 0.025)、肥大细胞(P = 0.03)和CD3 +淋巴细胞(P = 0.025)增加,但CD4 +或CD8 +淋巴细胞计数未增加。我们还检测到内皮细胞间黏附分子-1(P < 0.05)和E-选择素(P < 0.005)增加,但血管细胞黏附分子-1表达未增加,同时黏膜下和上皮LFA +白细胞相关增加(P < 0.01)。因此,在致敏哮喘患者中,支气管内局部滴注过敏原会导致气道黏膜炎症细胞浸润增加,这涉及微血管上表达的特定黏附分子的上调。