ICAM-1 and ICAM-2 Are Differentially Expressed and Up-Regulated on Inflamed Pulmonary Epithelium, but Neither ICAM-2 nor LFA-1: ICAM-1 Are Required for Neutrophil Migration Into the Airways In Vivo.
ICAM-1 and ICAM-2 Are Differentially Expressed and Up-Regulated on Inflamed Pulmonary Epithelium, but Neither ICAM-2 nor LFA-1: ICAM-1 Are Required for Neutrophil Migration Into the Airways In Vivo.
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DOI：
10.3389/fimmu.2021.691957
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发表时间：
2021
影响因子：
7.3
通讯作者：
Porter JC
中科院分区：
文献类型：
--
作者：
Chong DLW;Rebeyrol C;José RJ;Williams AE;Brown JS;Scotton CJ;Porter JC
神经元迁移到气道是抵抗感染的重要过程，并且由细胞粘附分子介导。细胞间粘附分子ICAM-1（CD 54）和ICAM-2（CD 102）是已知的中性粒细胞整联蛋白、淋巴细胞功能相关抗原（LFA）-1（αLβ2; CD 11 a/CD 18）和巨噬细胞-1抗原（Mac-1;αMβ2; CD 11b/CD 18）的配体，并参与白细胞向肺内的迁移。然而，它是不明确的中性粒细胞如何退出肺和跨上皮细胞迁移（TEPM）跨支气管或肺泡epithelium. We发现，人类和小鼠的肺泡上皮细胞表达ICAM-1，而支气管上皮细胞表达ICAM-2的作用ICAM-1，两者都上调在体外炎症刺激和炎症性肺病，如囊性纤维化。尽管β2整联蛋白在体外与ICAM-1和-2相互作用介导中性粒细胞穿过人支气管上皮迁移，但在体内脂多糖诱导的炎症过程中，ICAM-2和ICAM-1的LFA-1结合均不介导小鼠中性粒细胞迁移到肺或支气管肺泡间隙。此外，中性粒细胞本身的TEpM在体外导致上皮交界处渗透性增加和屏障功能降低。这表明，尽管与ICAM相互作用的β2整联蛋白可以调节健康肺中或上皮屏障完整时炎症早期的低水平嗜中性粒细胞运输;当上皮连接被破坏时，这些相互作用在炎症后期可能是多余的，并且不再限制TEpM。
Neutrophil migration into the airways is an important process to fight infection and is mediated by cell adhesion molecules. The intercellular adhesion molecules, ICAM-1 (CD54) and ICAM-2 (CD102) are known ligands for the neutrophil integrins, lymphocyte function associated antigen (LFA)-1 (αLβ2; CD11a/CD18), and macrophage-1 antigen (Mac-1;αMβ2;CD11b/CD18) and are implicated in leukocyte migration into the lung. However, it is ill-defined how neutrophils exit the lung and the role for ICAMs in trans-epithelial migration (TEpM) across the bronchial or alveolar epithelium. We found that human and murine alveolar epithelium expressed ICAM-1, whilst the bronchial epithelium expressed ICAM-2, and both were up-regulated during inflammatory stimulation in vitro and in inflammatory lung diseases such as cystic fibrosis. Although β2 integrins interacting with ICAM-1 and -2 mediated neutrophil migration across human bronchial epithelium in vitro, neither ICAM-2 nor LFA-1 binding of ICAM-1 mediated murine neutrophil migration into the lung or broncho-alveolar space during LPS-induced inflammation in vivo. Furthermore, TEpM of neutrophils themselves resulted in increased epithelial junctional permeability and reduced barrier function in vitro. This suggests that although β2 integrins interacting with ICAMs may regulate low levels of neutrophil traffic in healthy lung or early in inflammation when the epithelial barrier is intact; these interactions may be redundant later in inflammation when epithelial junctions are disrupted and no longer limit TEpM.
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影响因子：
8
作者：
Flemming, Sven;Luissint, Anny-Claude;Parkos, Charles A.
通讯作者：
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DOI：
10.1165/ajrcmb.23.3.4068
发表时间：
2000-09-01
影响因子：
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作者：
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影响因子：
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作者：
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