Human airway smooth muscle promotes human lung mast cell survival, proliferation, and constitutive activation: cooperative roles for CADM1, stem cell factor, and IL-6.
Human airway smooth muscle promotes human lung mast cell survival, proliferation, and constitutive activation: cooperative roles for CADM1, stem cell factor, and IL-6.
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DOI：
10.4049/jimmunol.181.4.2772
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发表时间：
2008-08-15
期刊：
影响因子：
--
通讯作者：
Bradding P
中科院分区：
文献类型：
--
作者：
Hollins F;Kaur D;Yang W;Cruse G;Saunders R;Sutcliffe A;Berger P;Ito A;Brightling CE;Bradding P
肥大细胞在特定组织区室中的微定位被认为对于许多不同疾病的病理生理学至关重要。这在哮喘中尤其明显，因为它们定位于气道平滑肌 (ASM) 束。肥大细胞被许多化学引诱剂招募到 ASM 并通过 CADM1 粘附，但其功能后果尚不清楚。在这项研究中，我们证明人 ASM 在体外维持人肺肥大细胞 (HLMC) 存活并诱导 HLMC 快速增殖。这需要细胞与细胞的接触，并通过 ASM 上表达的膜结合干细胞因子 (SCF)、可溶性 IL-6 和 HLMC 上表达的 CADM1 之间的协同相互作用来发生。 HLMC 中 CADM1 和 SCF 受体 (CD117) 之间存在物理相互作用，表明 CADM1 依赖性粘附促进膜结合 SCF 与其受体的相互作用。 HLMC-ASM 共培养还增强了 HLMC 脱颗粒，揭示了一种新型平滑肌驱动的、不依赖于过敏原的慢性肥大细胞激活机制。针对哮喘中的这些相互作用可能为治疗这种常见疾病提供新策略。
The microlocalization of mast cells within specific tissue compartments is thought to be critical for the pathophysiology of many diverse diseases. This is particularly evident in asthma where they localize to the airway smooth muscle (ASM) bundles. Mast cells are recruited to the ASM by numerous chemoattractants and adhere through CADM1, but the functional consequences of this are unknown. In this study, we show that human ASM maintains human lung mast cell (HLMC) survival in vitro and induces rapid HLMC proliferation. This required cell-cell contact and occurred through a cooperative interaction between membrane-bound stem cell factor (SCF) expressed on ASM, soluble IL-6, and CADM1 expressed on HLMC. There was a physical interaction in HLMC between CADM1 and the SCF receptor (CD117), suggesting that CADM1-dependent adhesion facilitates the interaction of membrane-bound SCF with its receptor. HLMC-ASM coculture also enhanced constitutive HLMC degranulation, revealing a novel smooth muscle-driven allergen-independent mechanism of chronic mast cell activation. Targeting these interactions in asthma might offer a new strategy for the treatment of this common disease.
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DOI：
10.1164/rccm.200312-1651oc
发表时间：
2004-09-15
影响因子：
24.7
作者：
Djukanovic, R;Wilson, SJ;Fahy, JV
通讯作者：
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DOI：
10.1165/ajrcmb.10.5.8179909
发表时间：
1994-05-01
影响因子：
6.4
作者：
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影响因子：
3
作者：
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Bradding P
影响因子：
14.2
作者：
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通讯作者：
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影响因子：
24.3
作者：
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