Galectin-3 plays a modulatory role in the life span and activation of murine neutrophils during early Toxoplasma gondii infection
Galectin-3 plays a modulatory role in the life span and activation of murine neutrophils during early Toxoplasma gondii infection
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DOI：
10.1016/j.imbio.2009.08.001
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发表时间：
2010-06-01
期刊：
影响因子：
2.8
通讯作者：
Mineo, Jose R.
中科院分区：
文献类型：
--
作者：
Alves, Celene M. O. S.;Silva, Deise A. O.;Mineo, Jose R.
半乳糖凝集素是参与多种生物过程的β-半乳糖苷结合凝集素，并且半乳糖凝集素-3（Gal-3）与免疫和炎症反应的调节有关。本研究旨在探讨Gal-3在弓形虫RH株体外感染过程中对小鼠中性粒细胞寿命和生物学功能的影响。在存在或不存在寄生虫的情况下培养来自C57 BL/6野生型（WT）和Gal-3敲除（KO）小鼠的炎性腹膜中性粒细胞（Nphi），并使用膜联蛋白-V和碘化丙啶染色分析磷脂酰丝氨酸（PS）暴露和细胞死亡，并通过MU测定分析细胞活力。细胞毒性测定乳酸脱氢酶（LDH），由溶菌酶释放脱粒，和细胞因子的产生在NO培养上清液中进行了测量。在Nphi培养物中测量佛波醇肉豆蔻酸酯乙酸酯（PMA）或酵母聚糖依赖性活性氧（ROS）。我们的研究结果表明，Gal-3参与了活Not的增加。数量和减少PS暴露和细胞死亡后T。弓形虫感染我们还观察到Gal-3下调了刚地诱导的Nphi毒性以及Nphi脱粒，而与感染无关。此外，Gal-3的表达与增加的IL-10的水平在开始和降低的TNF-α的水平以后，无论寄生虫感染，以及与降低的IL-6的水平和增加的IL-12的水平，在早期寄生虫感染。我们的研究结果还表明，Gal-3抑制PMA诱导的ROS产生，但不抑制酵母多糖诱导的ROS产生。弓形虫感染总之，Gal-3在弓形虫感染早期通过干扰Nphi的寿命和激活发挥重要的调节作用。(C)2009年Elsevier GmbH。All rights reserved.
Galectins are beta-galactoside-binding lectins involved in several biological processes and galectin-3 (Gal-3) is related to modulation of immune and inflammatory responses. This study aimed to evaluate the role of Gal-3 in the life span and biological functions of murine neutrophils during in vitro infection by virulent Toxoplasma gondii RH strain. Inflammatory peritoneal neutrophils (N phi) from C57BL/6 wildtype (WT) and Gal-3 knockout (KO) mice were cultured in the presence or absence of parasites and analyzed for phosphatidylserine (PS) exposure and cell death using Annexin-V and propidium iodide staining, and cell viability by MU assay. Cell toxicities determined by lactate dehydrogenase (LDH), degranulation by lysozyme release, and cytokine production were measured in NO culture supernatants. Phorbol myristate acetate (PMA)- or zymosan-dependent reactive oxygen species (ROS) were measured in N phi cultures. Our results demonstrated that Gal-3 is involved in the increase of the viable Not. number and the decrease of PS exposure and cell death following T. gondii infection. We also observed that Gal-3 downmodulates gondii-induced N phi toxicity as well as N phi degranulation regardless of infection. Furthermore, Gal-3 expression by N phi was associated with increased levels of IL-10 in the beginning and decreased levels of TNF-alpha later on, regardless of parasite infection, as well as with decreased levels of IL-6 and increased IL-12 levels, following early parasite infection. Our results also showed that Gal-3 suppresses PMA- but not zymosan-induced ROS generation in N phi following T. gondii infection. In conclusion, Gal-3 plays an important modulatory role by interfering in N phi life span and activation during early T gondii infection. (C) 2009 Elsevier GmbH. All rights reserved.