Holgate S T, Church M K, Howarth P H, Morton E N, Frew A J, Djukanović R
University Medicine, Southampton General Hospital, UK.
Int Arch Allergy Immunol. 1995 May-Jun;107(1-3):29-33. doi: 10.1159/000236921.
The clear recognition that asthma has an inflammatory basis has led to a search for genetic and environmental causes. Genetic linkage studies provide evidence for allelic association between polymorphic markers of interleukin-9 on chromosome 5 and a principal component of the allergic phenotype, log IgE. Further studies that intrauterine environmental factors are an important determinant of the allergic phenotype in addition to allergen exposure during the first year of life. Once sensitised, the respiratory mucosa provides the allergic interface between the environment and internal milieux involving autacoid and cytokine release from mast cells. Up-regulation of endothelial cell adhesion molecules, specifically E-selectin and ICAM-1, is responsible for the leucocyte recruitment of the late-phase asthmatic response, while recruitment of T cells and their subsequent activation contribute to the ongoing inflammatory response of asthma. The epithelium is the origin and target tissue for the inflammatory response, resulting in detachment of suprabasal cells, up-regulation of adhesion molecules and enhanced mediator and cytokine secretion. These latter findings, being more evident in severe chronic disease, suggest that the 'formed' airway elements are also important in mediating the ongoing inflammation characteristic of asthma.
对哮喘具有炎症基础的明确认识引发了对遗传和环境病因的探寻。基因连锁研究为5号染色体上白细胞介素-9的多态性标记与过敏表型的主要成分——对数免疫球蛋白E（log IgE）之间的等位基因关联提供了证据。进一步的研究表明，除生命第一年接触变应原外，宫内环境因素也是过敏表型的重要决定因素。一旦致敏，呼吸道黏膜就成为环境与内部环境之间的过敏界面，涉及肥大细胞释放自身活性物质和细胞因子。内皮细胞黏附分子，特别是E-选择素和细胞间黏附分子-1（ICAM-1）的上调，负责迟发性哮喘反应中的白细胞募集，而T细胞的募集及其随后的激活则促成哮喘持续的炎症反应。上皮是炎症反应的起源和靶组织，导致基底层上细胞脱离、黏附分子上调以及介质和细胞因子分泌增加。这些在严重慢性疾病中更为明显的发现表明，“已形成的”气道成分在介导哮喘持续炎症特征方面也很重要。
