NKG2D ligands are expressed on stressed human airway epithelial cells
NKG2D ligands are expressed on stressed human airway epithelial cells
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DOI：
10.1152/ajplung.00327.2005
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发表时间：
2006-08-01
影响因子：
4.9
通讯作者：
Cosman, David
中科院分区：
文献类型：
--
作者：
Borchers, Michael T.;Harris, Nathaniel L.;Cosman, David
气道的免疫监视对于维持肺的完整性和健康至关重要。我们已经确定了一个在应激气道上皮细胞表面表达的配体家族，其功能是结合在几种肺淋巴细胞（包括自然杀伤细胞、γ δ（+）T细胞和CD 8（+）T细胞）上发现的NKG 2D激活受体。我们在正常和转化的气道上皮细胞中采用实时PCR和流式细胞术来证明主要组织相容性复合物I类链相关（MIC）B和UL-16结合蛋白（ULBP）配体（ULBP 1 -4）在所有细胞系中以mRNA水平普遍表达。云母/B表面表达存在于70%的转化细胞系上，但在原代细胞上检测不到。我们证明，云母/B和ULBP 1，2，3和4的表达是罕见的或不存在的未刺激的正常人支气管上皮细胞的细胞表面上，虽然转录本和细胞内蛋白质存在。正常人支气管上皮细胞暴露于0.3 mM过氧化氢表现出诱导的细胞表面上检查的所有配体。表面表达不依赖于转录水平或总细胞蛋白的变化，并且由有丝分裂原活化蛋白激酶的ERK家族介导。应激气道上皮细胞上NKG 2D配体的诱导代表了免疫细胞活化在肺健康和疾病调节中的潜在重要机制。
Immune surveillance of the airways is critical to maintain the integrity and health of the lung. We have identified a family of ligands expressed on the surface of stressed airway epithelial cells whose function is to bind the NKG2D-activating receptor found on several pulmonary lymphocytes, including natural killer cells, gamma delta(+) T cells, and CD8(+) T cells. We employed real-time PCR and flow cytometry in normal and transformed airway epithelial cell to demonstrate that major histocompatibility complex class I chain-related (MIC) B and the UL-16 binding protein (ULBP) ligands (ULBP1-4) are ubiquitously expressed at the mRNA level in all cell lines. MICA/B surface expression was present on 70% of transformed cell lines but was undetectable on primary cells. We demonstrate that MICA/B and ULBP 1, 2, 3, and 4 expression is rare or absent on the cell surface of unstimulated normal human bronchial epithelial cells although transcripts and intracellular proteins are present. Normal human bronchial epithelial cells exposed to 0.3 mM hydrogen peroxide exhibit an induction of all ligands examined on the cell surface. Surface expression is independent of changes in transcript level or total cellular protein and is mediated by the ERK family of mitogen-activated protein kinases. The induction of NKG2D ligands on stressed airway epithelial cells represents a potentially important mechanism of immune cell activation in regulation of pulmonary health and disease.