Pathophysiology of the inflammatory response
Pathophysiology of the inflammatory response
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DOI：
10.1016/s0091-6749(99)70308-8
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发表时间：
1999-10-01
影响因子：
14.2
通讯作者：
Pearlman, DS
中科院分区：
文献类型：
--
作者：
Pearlman, DS
气道过敏反应涉及多种细胞和多种化学介质，这些细胞和化学介质导致过敏性鼻炎和哮喘的临床症状。体外和动物模型实验以及越来越多的特应性人类受试者研究，揭示了导致气道过敏性炎症的细胞活动的协调连续体在遗传易感个体中首次暴露于新抗原该致敏步骤可能依赖于T（H）2淋巴细胞的分化和细胞因子释放。在T（H）2衍生的细胞因子中，IL-4有效地增强B淋巴细胞产生免疫球蛋白E抗体。这些抗体与气道肥大细胞上的特异性受体的附着为随后的抗原暴露的急性炎症反应奠定了基础，因为结合抗原引起的IgE交联激活肥大细胞释放许多炎症介质。这些肥大细胞衍生的介质通过增强血管渗漏、支气管痉挛和与副交感神经反射相关的伤害性神经元的激活共同产生急性期临床症状。同时，一些肥大细胞介质上调白细胞（嗜酸性粒细胞，以及嗜碱性粒细胞和淋巴细胞）的粘附分子在内皮细胞上的表达，所述粘附分子是晚期过敏反应中的小桶元件。在急性期释放的化学引诱剂分子将这些白细胞在相对无炎症的募集期吸引到气道，在那里它们随后释放过多的细胞因子和组织损伤蛋白酶，这预示着第二波气道炎性创伤（晚期反应）。这些过程的重复，以及可能在气道粘膜中建立由旁分泌和自分泌细胞因子刺激维持的记忆T淋巴细胞和嗜酸性粒细胞，可能导致气道超敏反应和慢性气道症状。
Airway allergic reactions enlist diverse cells and a multitude of chemical mediators that are responsible for the clinical symptoms of allergic rhinitis and asthma, Experiments in vitro and in animal models, as well as increasingly numerous studies in atopic human subjects, are revealing that an orchestrated continuum of cellular activities leading to airway allergic inflammation is set in motion in genetically predisposed individuals at the first exposure to a novel antigen. This sensitization step likely depends on differentiation of and cytokine release by T(H)2 lymphocytes, Among T(H)2-derived cytokines, IL-4 potently enhances B-lymphocyte generation of immunoglobulin E antibodies. The attachment of these antibodies to specific receptors on airway mast cells sets the stage for an acute inflammatory response on subsequent antigen exposure because IgE crosslinking by a bound antigen activates mast cells to release numerous inflammatory mediators. These mast cell-derived mediators collectively produce acute-phase clinical symptoms by enhancing vascular leak, bronchospasm, and activation of nociceptive neurons linked to parasympathetic reflexes, Simultaneously, some mast cell mediators up-regulate expression on endothelial cells of adhesion molecules for leukocytes (eosinophils, but also basophils and lymphocytes), which are keg elements in the late-phase allergic response. Chemoattractant molecules released during the acute phase draw these leukocytes to airways during a relatively symptom-free recruitment phase, where they later release a plethora of cytokines and tissue-damaging proteases that herald a second wave of airway inflammatory trauma (late-phase response). The repetition of these processes, with the possible establishment in airway mucosa of memory T lymphocytes and eosinophils that are maintained by paracrine and autocrine cytokine stimulation, may account for airway hypersensitivity and chronic airway symptoms.