NOD mice have a severly impaired ability to recruit leukocytes into sites of inflammation
NOD mice have a severly impaired ability to recruit leukocytes into sites of inflammation
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DOI：
10.1002/eji.200425513
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发表时间：
2005-01-01
影响因子：
5.4
通讯作者：
Versnel, MA
中科院分区：
文献类型：
--
作者：
Bouma, G;Nikolic, T;Versnel, MA
巨噬细胞（MPhi）和树突状细胞（DC）在胰腺中的积累在自身免疫性糖尿病的发病机制中起着至关重要的作用。我们研究了单核细胞、MPhi和DC向炎症部位的募集，即在自身免疫性糖尿病的NOD小鼠模型中的腹膜腔和皮下引起的气囊。在注射巯基乙酸盐（腹膜）、C5 a（腹膜、气囊）、CCL 2和CCL 3（气囊）后1 - 7天研究白细胞募集。C57 BL/6和BALB/c小鼠作为对照。对募集的细胞进行形态学和流式细胞术分析，测量渗出液中的IL-1 β、TNF-α、IL-6、IL-12和IL-10，并测定渗出液MPhi（Boyden室）的体外CCL 2-趋化性。NOD小鼠在MPhi、DC、单核细胞和粒细胞的募集方面严重受损。NOD小鼠气囊注射趋化因子后，IL-10水平升高，IL-1 β水平降低，而其他细胞因子正常或极低表达。此外，NOD渗出液MPhi显示受损的体外CCL 2诱导的迁移。我们的数据表明，NOD小鼠有一个受损的能力，招募白细胞进入炎症部位引起的腹膜和气囊。在这些位点升高的IL-10/ IL-1 β比值和NOD单核细胞迁移能力的不足是这种损伤的重要决定因素。
The accumulation of macrophages (MPhi) and dendritic cells (DC) in the pancreas plays a crucial role in the pathogenesis of autoimmune diabetes. We studied the recruitment of monocytes, MPhi and DC to sites of inflammation, i.e. the peritoneal cavity and a subcutaneously elicited air pouch in the NOD mouse model of autoimmune diabetes. The leukocyte recruitment was studied from 1 to 7 days after injection of thioglycollate (peritoneum), C5a (peritoneum, air pouch), CCL2 and CCL3 (air pouch). C57BL/6 and BALB/c mice served as controls. Morphological and flow cytometric analysis of the recruited cells was performed, IL-1beta, TNF-alpha, IL-6, IL-12 and IL-10 in exudates measured, and in vitro CCL2-chemotaxis of exudate MPhi (Boyden chamber) determined. NOD mice were strongly impaired in the recruitment of MPhi, DC, monocytes, and granulocytes. Chemokine-injected air pouches of NOD mice showed an increased IL-10 and a decreased IL-1beta level, while the other cytokines were normally or very lowly expressed. In addition, NOD exudate MPhi displayed an impaired in vitro CCL2-induced migration. Our data show that NOD mice have an impaired ability to recruit leukocytes into sites of inflammation elicited in the peritoneum and the air pouch. A raised IL-10/ IL-1beta ratio at these sites and a deficient migratory capacity of NOD monocytes are important determinants in this impairment.