A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs.
A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs.
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DOI：
10.4049/jimmunol.0902199
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发表时间：
2010-03-15
期刊：
影响因子：
--
通讯作者：
Kaplan MJ
中科院分区：
文献类型：
--
作者：
Denny MF;Yalavarthi S;Zhao W;Thacker SG;Anderson M;Sandy AR;McCune WJ;Kaplan MJ
由于单核细胞组分中存在低密度粒细胞（LDG），因此在狼疮患者PBMC微阵列中富含嗜中性粒细胞特异性基因。这些LDG的功能和致病性尚未得到表征。我们开发了一种从狼疮PBMC中纯化LDG的技术，并评估了其表型、功能和在疾病发病机制中的潜在作用。比较LDG、其自体狼疮中性粒细胞和健康对照中性粒细胞的杀微生物和吞噬能力、活性氧的产生、活化状态、炎性细胞因子谱和I型IFN表达和特征。LDG杀死内皮细胞的能力和它们的抗血管生成潜力也被评估。LDG表现出活化的表型，分泌增加水平的I型IFN、TNF-α和IFN-γ，但表现出受损的吞噬能力。LDG诱导显著的内皮细胞细胞毒性并合成足够水平的I型IFN以破坏内皮祖细胞分化成成熟内皮细胞的能力。此外，LDG消耗恢复内皮祖细胞的功能能力。我们的结论是狼疮LDGs是促炎性的，并显示致病特征，包括合成I型IFN的能力。它们可能通过同时介导增强的血管损伤和抑制血管修复，在SLE的过早心血管疾病发展中发挥重要的双重作用。
Neutrophil-specific genes are abundant in PBMC microarrays from lupus patients due to presence of low density granulocytes (LDGs) in mononuclear cell fractions. The functionality and pathogenicity of these LDGs have not been characterized. We developed a technique to purify LDGs from lupus PBMCs and assessed their phenotype, function and potential role in disease pathogenesis. LDGs, their autologous lupus neutrophils and healthy control neutrophils were compared in their microbicidal and phagocytic capacities, generation of reactive oxygen species, activation status, inflammatory cytokine profile and type I IFN expression and signatures. The capacity of LDGs to kill endothelial cells and their antiangiogenic potential were also assessed. LDGs display an activated phenotype, secrete increased levels of type I IFNs, TNF-α and IFN-γ, but show impaired phagocytic potential. LDGs induce significant endothelial cell cytotoxicity and synthesize sufficient levels of type I IFNs to disrupt the capacity of endothelial progenitor cells to differentiate into mature endothelial cells. Further, LDG depletion restores the functional capacity of endothelial progenitor cells. We conclude that lupus LDGs are proinflammatory and display pathogenic features, including the capacity to synthesize type I IFNs. They may play an important dual role in premature cardiovascular disease development in SLE by simultaneously mediating enhanced vascular damage while inhibiting vascular repair.
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影响因子：
--
作者：
ADERKA, D;WYSENBEEK, A;WALLACH, D
通讯作者：
WALLACH, D
影响因子：
6.5
作者：
Eriksen, KW;Lovato, P;Odum, N
通讯作者：
Odum, N
DOI：
10.1073/pnas.82.24.8737
发表时间：
1985-12-01
影响因子：
11.1
作者：
CONNELLY, JC;SKIDGEL, RA;ERDOS, EG
通讯作者：
ERDOS, EG
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
5.5
作者：
Chen, M. -J.;Tseng, H. -M.;Huang, J. -L.
通讯作者：
Huang, J. -L.