Monocytes are resistant to apoptosis in systemic juvenile idiopathic arthritis

被引：20

作者：

Srivastava, Shivani ^{[2
]}

Macaubas, Claudia

Deshpande, Chetan

Alexander, Heather C. ^{[3
]}

Chang, Sheng-Yung ^{[3
]}

Sun, Yue

Park, Jane L. ^{[4
]}

Lee, Tzielan ^{[4
]}

Begovich, Ann ^{[3
]}

Mellins, Elizabeth D. ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Pediat, Program Immunol, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[3] Celera, Alameda, CA USA

[4] Stanford Univ, Dept Pediat, Div Pediat Rheumatol, Stanford, CA 94305 USA

来源：

CLINICAL IMMUNOLOGY | 2010年 / 136卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Systemic juvenile arthritis; Monocytes; Apoptosis; MIGRATION INHIBITORY FACTOR; MACROPHAGE ACTIVATION SYNDROME; TUMOR-NECROSIS-FACTOR; CELL-DEATH APOPTOSIS; RHEUMATOID-ARTHRITIS; PERIPHERAL-BLOOD; FAS LIGAND; GENE-EXPRESSION; ALVEOLAR MACROPHAGES; CASPASE-8; ACTIVATION;

D O I：

10.1016/j.clim.2010.04.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We investigated whether circulating monocytes from patients with systemic juvenile idiopathic arthritis (SJIA) are resistant to apoptosis and which apoptotic pathway(s) may mediate this resistance. A microarray analysis of peripheral blood mononuclear cells (PBMC) of SJIA samples and RT-PCR analysis of isolated monocytes showed that monocytes from active SJIA patients express transcripts that imply resistance to apoptosis. SJIA monocytes incubated in low serum show reduced annexin binding and diminished FasL up-regulation compared to controls. SJIA monocytes are less susceptible to anti-Fas-induced apoptosis and, upon activation of the mitochondrial pathway with staurosporine, show diminished Bid cleavage and Bcl-w down-regulation compared to controls. Exposure to SJIA plasma reduces responses to apoptotic triggers in normal monocytes. Thus, SJIA monocytes are resistant to apoptosis due to alterations in both the extrinsic and intrinsic apoptosis pathways, and circulating factors associated with active SJIA may confer this phenotype. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：257 / 268

页数：12

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