Sorting out the cytokines of asthma.
Sorting out the cytokines of asthma.
复制标题
分类哮喘的细胞因子。
DOI：
10.1084/jem.183.1.1
复制
发表时间：
1996-01-01
影响因子：
15.3
通讯作者：
Austen, KF
中科院分区：
文献类型：
--
作者：
Drazen, JM;Arm, JP;Austen, KF
哮喘是一种复杂的疾病，其特征是间歇性、可逆性气道阻塞以及气道高反应性和炎症。尽管其病因尚不清楚，但我们现在认识到哮喘是一种综合征，其常见的病理表现是气道炎症。即使患有轻度哮喘的患者也会出现气道发炎，一些数据表明哮喘的严重程度与炎症的程度相关 (1-3)。哮喘气道炎症的独特之处在于，气道壁被具有 2 型辅助 T 表型的 T 淋巴细胞 (4) 以及嗜酸性粒细胞和肥大细胞 (2,5,6) 浸润。这些细胞中的每一种都被认为会导致哮喘特有的生理变化（图 1）。 TH2 淋巴细胞产生一组有限的细胞因子，包括 IL-3、IL-4、IL-5 和 GM-CSF。尽管尚未确定导致该淋巴细胞亚群浸润哮喘气道的主要信号，但基于以下概念提出了许多模型：炎症过程是通过在适当的细胞因子存在下呈现一组受限抗原来触发的。该微环境中抗原呈递的净效应是通过 IL-4 对 Ig 同种型转换的作用促进 IgE 的合成 (7)，并通过 GMCSF、IL-3 和 IL-5 的作用增强嗜酸性粒细胞的分化、迁移和病理能力 (8, 9)。哮喘气道中产生的 IgE 与肥大细胞上的 Fc~RI 结合，启动它们被抗原激活。肥大细胞源自骨髓前体，以非异染染色、无颗粒、CD34+、c-kit+ 和 F% I< I+ 单核白细胞的形式进入循环 (10)，并定位于粘膜和粘膜下部位，例如支气管。一旦定位，这些谱系定向的未成熟肥大细胞就会经历组织特异性分化以及成熟和扩张。它们的发育和运动涉及来自微环境中的结构细胞和造血细胞的生长因子和细胞因子。肥大细胞进一步迁移到管腔空间，并可以通过支气管肺泡灌洗来恢复，为增强的激活反应做好准备 (11)。肥大细胞还产生 IL-4 (12, 13)（有利于 T 细胞转化为 TH 2 表型）和 IL-5 (14)（有助于嗜酸性粒细胞生成和启动嗜酸性粒细胞以增强反应）。一旦从循环系统中募集出来，成熟的嗜酸性粒细胞在“哮喘”细胞因子存在的情况下，会转化为自身攻击性表型 (15, 16)，称为“hy-
A sthma is a complex disorder characterized by intermittent, reversible airway obstruction, and by airway hyperresponsiveness and inflammation. Although its cause (s) remain unknown, we now recognize that asthma is a syndrome whose common pathologic expression is inflammation of the airways. The airways of patients with even mild asthma are inflamed, and some data suggest that the severity of the asthma parallels the degree of inflammation (1-3). The airway inflammation of asthma is unique in that the airway wall is infiltrated by T lymphocytes bearing the T helper type 2 phenotype (4) and by eosinophils and mast ceils (2, 5, 6). Each of these cells is thought to contribute to the physiologic changes that characterize asthma (Fig. 1). The TH2 lymphocytes produce a limited panel ofcytokines including IL-3, IL-4, IL-5, and GM-CSF. Although the primary signals resulting in the infiltration of the asthmatic airways by this lymphocyte subset have not yet been identified, a number of models have been proposed based on the concept that the inflammtory process is triggered by the presentation of a restricted panel of antigens in the presence of appropriate cytokines. The net effect of antigen presentation in this microenvironment is to promote the synthesis of IgE through the actions of IL-4 on Ig isotype switching (7) and to enhance the differentiation, migration, and pathobiologic capacity of eosinophils through the actions of GMCSF, IL-3, and IL-5 (8, 9). The IgE produced in asthmatic airways binds to Fc~ RI on mast cells, priming them for activation by antigen. Mast cells arise from bone marrow precursors, enter the circulation as non-metachromatically staining, agranular, CD34+, c-kit+, and F% I< I+ mononuclear leukocytes (10), and localize to mucosal and submucosal sites such as the bronchi. Once localized, these lineage-committed immature mast cells undergo tissue-specific differentiation along with maturation and expansion. Their development and movement involves growth factors and cytokines derived from both structural and hematopoietic cells in their microenvironment. The mast cells that further migrate into the luminal space, and which can be recovered by bronchoalveolar lavage, are primed for an augmented activation response (11). Mast cells also elaborate IL-4 (12, 13), which favors conversion ofT cells to the TH 2 phenotype, and IL-5 (14), which contributes to eosinophilopoiesis and to the priming of eosinophils for augmented responses. Once recruited from the circulation, mature eosinophils, in the presence of" asthmatic" cytokines, convert to an autoaggressive phenotype (15, 16), termed" hy-
登录
查看更多内容
白介素5缺乏消除小鼠哮喘模型中的嗜酸性粒细胞，气道高反应性和肺损伤。
影响因子：
15.3
作者：
Foster, PS;Hogan, SP;Ramsay, AJ;Matthaei, KI;Young, IG
通讯作者：
Young, IG
影响因子：
6
作者：
FLINT, KC;LEUNG, KBP;JOHNSON, NM
通讯作者：
JOHNSON, NM
DOI：
10.1111/j.1749-6632.1994.tb39791.x
发表时间：
1994-01-01
期刊：
CELLS AND CYTOKINES IN LUNG INFLAMMATION
影响因子：
--
作者：
HOWARTH, PH;BRADDING, P;HOLGATE, ST
通讯作者：
HOLGATE, ST
DOI：
10.1164/ajrccm/141.6.1453
发表时间：
1990-06-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
LEE, TH;CREA, AEG;SERHAN, CN
通讯作者：
SERHAN, CN
影响因子：
64.5
作者：
BROWN, MA;PIERCE, JH;PAUL, WE
通讯作者：
PAUL, WE