HUMAN EOSINOPHILS CAN EXPRESS THE CYTOKINES TUMOR-NECROSIS-FACTOR-ALPHA AND MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA

HUMAN EOSINOPHILS CAN EXPRESS THE CYTOKINES TUMOR-NECROSIS-FACTOR-ALPHA AND MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA
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DOI:
10.1172/jci116506
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发表时间:
1993-06-01
影响因子:
15.9
通讯作者:
GALLI, SJ
GALLI, SJ
中科院分区:
医学1区
文献类型:
--
作者:
COSTA, JJ;MATOSSIAN, K;GALLI, SJ

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通过原位杂交,44-100%的血液嗜酸性粒细胞从5例嗜酸性粒细胞增多症患者和4名正常人表现出强烈的杂交信号TNF-α mRNA。TNF-α蛋白可通过免疫组化检测到的嗜酸性粒细胞的血液嗜酸性粒细胞的高嗜酸性粒细胞,和纯化的血液嗜酸性粒细胞从三个特应性供体表现出放线菌酮的自发释放TNF-α在体外。高嗜酸性粒细胞供体的许多血液嗜酸性粒细胞(39-91%)显示出巨噬细胞炎性蛋白-1 α(MIP-1 α)mRNA的强标记,而正常供体的嗜酸性粒细胞仅显示出弱或不可检测的MIP-1 α mRNA杂交信号。大多数鼻息肉组织中浸润的嗜酸性粒细胞TNF-α和MIP-1 α mRNA均呈强阳性。通过北方印迹分析,来自特发性嗜酸性粒细胞增多综合征患者的高度富集的血液嗜酸性粒细胞显示出TNF-α和MIP-1 α mRNA的差异表达。这些发现表明,人嗜酸性粒细胞是TNF-α和MIP-1 α的潜在来源,在嗜酸性粒细胞过多供体的血液嗜酸性粒细胞和嗜酸性粒细胞浸润鼻息肉中,两种细胞因子的mRNA表达水平较高,正常受试者的嗜酸性粒细胞表达的TNF-α水平高于MIP-1 α mRNA,并且从特应性供体的血液中纯化的嗜酸性粒细胞可以在体外释放TNF-α。
By in situ hybridization, 44-100% of the blood eosinophils from five patients with hypereosinophilia and four normal subjects exhibited intense hybridization signals for TNF-alpha mRNA. TNF-alpha protein was detectable by immunohistochemistry in blood eosinophils of hypereosinophilic subjects, and purified blood eosinophils from three atopic donors exhibited cycloheximide-inhibitable spontaneous release of TNF-alpha in vitro. Many blood eosinophils (39-91%) from hypereosinophilic donors exhibited intense labeling for macrophage inflammatory protein-1alpha (MIP-1alpha) mRNA, whereas eosinophils of normal donors demonstrated only weak or undetectable hybridization signals for MIP-1alpha mRNA. Most tissue eosinophils infiltrating nasal polyps were strongly positive for both TNF-alpha and MIP-1alpha mRNA. By Northern blot analysis, highly enriched blood eosinophils from a patient with the idiopathic hypereosinophilic syndrome exhibited differential expression of TNF-alpha and MIP-1alpha mRNA. These findings indicate that human eosinophils represent a potential source of TNF-alpha and MIP-1alpha, that levels of expression of mRNA for both cytokines are high in the blood eosinophils of hypereosinophilic donors and in eosinophils infiltrating nasal polyps, that the eosinophils of normal subjects express higher levels of TNF-alpha than MIP-1alpha mRNA, and that eosinophils purified from the blood of atopic donors can release TNF-alpha in vitro.