GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR CONTRIBUTES TO ENHANCED MONOCYTE SURVIVAL IN CHRONIC ATOPIC-DERMATITIS
GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR CONTRIBUTES TO ENHANCED MONOCYTE SURVIVAL IN CHRONIC ATOPIC-DERMATITIS
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DOI：
10.1172/jci117642
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发表时间：
1995-01-01
影响因子：
15.9
通讯作者：
LEUNG, DYM
中科院分区：
文献类型：
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作者：
BRATTON, DL;HAMID, Q;LEUNG, DYM
有证据表明效应细胞存活时间延长可能导致炎症持续存在，这促使我们思考单核巨噬细胞（慢性特应性皮炎 (AD) 病变中的主要炎症细胞）是否会在 AD 中表现出更高的存活率。对来自慢性 AD、银屑病患者和正常 (NL) 供体的外周血单核细胞培养物进行了检查，以了解经历细胞凋亡（程序性细胞死亡）过程的细胞的形态特征和 DNA 碎片特征。 AD单核细胞培养物的细胞凋亡发生率显着低于NL单核细胞培养物（45% vs 68%，P < 0.01）或银屑病单核细胞培养物（45 vs 80%，P < 0.01）。此外，与培养的NL单核细胞相比，AD单核细胞对细胞凋亡抑制剂IL-1和细胞凋亡增强剂IL-4均无反应。值得注意的是，GM-CSF 以浓度依赖性方式降低了 NL 单核细胞培养物中细胞凋亡的发生率，并使它们对这些细胞因子无反应。这些发现表明 GM-CSF 可能会增强 AD 中单核细胞的存活率。为了支持这一假设，AD 单核细胞培养物产生的 GM-CSF 比 NL 单核细胞或银屑病单核细胞培养物多五倍（P < 0.05）。此外，通过原位杂交，在慢性 AD 皮损活检中检测到的 GM-CSF mRNA 表达细胞数量明显多于急性 AD 或 NL 皮肤（P < 0.05）。最后，NL 单核细胞与从 AD 患者单核细胞获得的上清液一起孵育，表现出显着的细胞凋亡抑制作用，这种作用可以被 GM-CSF 的中和抗体消除。总而言之，这些数据强烈表明，AD 患者细胞产生的 GM-CSF 增加会抑制单核细胞凋亡，并可能导致这种炎症性疾病的慢性化。
Evidence suggesting that prolonged effector cell survival may contribute to perpetuation of inflammation prompted us to ask whether monocyte macrophages, the predominate inflammatory cell in the lesion of chronic atopic dermatitis (AD), exhibit enhanced survival in AD. Cultures of peripheral blood monocytes from patients with chronic AD, psoriasis, and from normal (NL) donors were examined for morphologic features and DNA fragmentation characteristic of cells undergoing the process of apoptosis (programmed cell death). Cultures of AD monocytes exhibited a significantly lower incidence of apoptosis than did cultures of NL monocytes (45 vs 68%, P < 0.01), or psoriatic monocytes (45 vs 80%, P < 0.01). Furthermore, AD monocytes were unresponsive to both IL-1, an inhibitor of apoptosis, and IL-4, an enhancer of apoptosis, in comparison to cultured NL monocytes. Of note, GM-CSF in a concentration-dependent fashion, decreased the incidence of apoptosis in NL monocyte cultures and rendered them unresponsive to these cytokines. These findings suggested that GM-CSF may enhance monocyte survival in AD. In support of this hypothesis, AD monocyte cultures produced fivefold more GM-CSF than did cultures of NL monocytes or psoriatic monocytes (P < 0.05). Additionally, there was a significantly greater number of GM-CSF mRNA expressing cells detected by in situ hybridization in biopsies of lesions of chronic AD than in acute AD or NL skin (P < 0.05). Finally, NL monocytes incubated with supernatants obtained from monocytes of AD patients exhibited significant inhibition of apoptosis, an effect that could be ablated by a neutralizing antibody to GM-CSF. Taken together, these data strongly suggest that increased production of GM-CSF by cells from patients with AD inhibits monocyte apoptosis and may contribute to the chronicity of this inflammatory disease.