A CD18/ICAM-1-dependent pathway mediates eosinophil adhesion to human bronchial epithelial cells
A CD18/ICAM-1-dependent pathway mediates eosinophil adhesion to human bronchial epithelial cells
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DOI：
10.1165/ajrcmb.19.3.3179
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发表时间：
1998-09-01
影响因子：
6.4
通讯作者：
Hellewell, PG
中科院分区：
文献类型：
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作者：
Burke-Gaffney, A;Hellewell, PG
嗜酸性粒细胞粘附于气道上皮被认为促进嗜酸性粒细胞在哮喘气道中的积累和滞留。针对细胞间粘附分子 1 (ICAM-1) 及其 CD18 白细胞整合素配体的单克隆抗体 (mAb) 已被证明可以抑制哮喘动物模型中的气道嗜酸性粒细胞增多，尽管该途径在嗜酸性粒细胞-上皮粘附中的作用尚不完全清楚。为了研究 CD18 和 ICAM-1 的体外作用，我们测量了荧光标记的人嗜酸性粒细胞与用培养基（低组成型 ICAM-1）或肿瘤坏死因子-α（TNF-α；1 ng/ml）和干扰素-γ（IFN-γ）（10 ng/ml；增加 ICAM-1）预处理 24 小时的正常人支气管上皮细胞（NHBEC）单层的粘附。用 C5a (10(-7) M) 刺激嗜酸性粒细胞，30 分钟时测量到未激活的 NHBEC 的粘附力从 11.4 +/- 0.7 增加到 15.5 +/- 0.4% (n = 4)，并且这种增加不依赖于 CD18/ICAM-1，而醋酸佛波醇酯 (PMA) (10(-8) M) 诱导的粘附力 (20.7 +/-) 1.7%）被抗CD18消除并被抗ICAM-1降低。相反，C5a和PMA诱导的对TNF-α/IFN-γ激活的NHBEC的粘附（分别从11.1+/-1.3%增加到21.9+/-1.0%和27.6+/-1.9%）是CD18-和ICAM-1依赖性的。 Eotaxin（但不受正常 T 细胞表达和分泌的激活调节）、巨噬细胞炎症蛋白 1、甲酰甲硫氨酰亮氨酰苯丙氨酸、白三烯 B-4 或血小板激活因子也诱导 CD 18/ICAM-1 依赖性粘附到激活的 NHBEC 上。在不添加化学引诱剂的情况下，嗜酸性粒细胞对 NHBEC 的粘附随着时间的推移而增加，并且在 120 分钟时，活化的 NHBEC（37.3 +/- 2.4%，n = 5）显着高于未活化的单层细胞（24.3 +/- 1.9%）（P < 0.01）；针对 CD18 或 ICAM-1 的 mAb 消除了增加的粘附，但不是基础的粘附。这些结果表明 CD18/ICAM-1 介导嗜酸性粒细胞对活化的 NHBEC 的粘附，但对静息 NHBEC 的粘附在很大程度上独立于该途径。
Eosinophil adhesion to airway epithelium is believed to facilitate eosinophil accumulation and retention in asthmatic airways. Monoclonal antibodies (mAb) against intercellular adhesion molecule-1 (ICAM-1) and its CD18 leukocyte integrin ligands have been shown to inhibit airway eosinophilia in animal models of asthma, although the role of this pathway in eosinophil-epithelial adhesion is not fully understood. To investigate the role in vitro of CD18 and ICAM-1, we measured adhesion of fluorescently labeled human eosinophils to normal human bronchial epithelial cell (NHBEC) monolayers pretreated for 24 h with culture medium (low constitutive ICAM-1) or tumor necrosis factor-alpha (TNF-alpha; 1 ng/ml) and interferon-gamma (IFN-gamma) (10 ng/ml; increased ICAM-1). Stimulation of eosinophils with C5a (10(-7) M) increased adhesion measured at 30 min to unactivated NHBEC from 11.4 +/- 0.7 to 15.5 +/- 0.4% (n = 4), and this increase was CD18/ICAM-1-independent, whereas phorbolmyristate acetate (PMA) (10(-8) M)-induced adhesion (20.7 +/- 1.7%) was abolished by anti-CD18 and reduced by anti-ICAM-1. In contrast, C5a- and PMA-induced adhesion to TNF-alpha/IFN-gamma-activated NHBEC (increased from 11.1 +/- 1.3% to 21.9 +/- 1.0% and 27.6 +/- 1.9%, respectively) was CD18- and ICAM-1-dependent. Eotaxin, but not regulated on activation normal T cells expressed and secreted, macrophage inflammatory protein-1, formyl methionyl leucyl phenylalanine, leukotriene B-4 or platelet-activating factor, also induced CD 18/ICAM-1-dependent adhesion to activated NHBEC. In the absence of added chemoattractants, eosinophil adhesion to NHBEC increased with time and, at 120 min, was significantly greater (P < 0.01) to activated NHBEC (37.3 +/- 2.4%, n = 5) than to unactivated monolayers (24.3 +/- 1.9%); mAb against CD18 or ICAM-1 abolished increased, but not basal, adhesion. These results suggest that CD18/ICAM-1 mediated eosinophil adhesion to activated NHBEC but that adhesion to resting NHBEC was largely independent of this pathway.