The acute-phase protein α1-acid glycoprotein (AGP) induces rises in cytosolic Ca2+ in neutrophil granulocytes via sialic acid binding immunoglobulin-like lectins (Siglecs)
The acute-phase protein α1-acid glycoprotein (AGP) induces rises in cytosolic Ca2+ in neutrophil granulocytes via sialic acid binding immunoglobulin-like lectins (Siglecs)
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DOI：
10.1096/fj.07-8534com
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发表时间：
2007-12-01
期刊：
影响因子：
4.8
通讯作者：
Grenegard, Magnus
中科院分区：
文献类型：
--
作者：
Gunnarsson, Peter;Levander, Louise;Grenegard, Magnus
我们研究了急性期蛋白α 1-酸性糖蛋白（AGP）是否诱导中性粒细胞[Ca 2 +] i升高，并试图鉴定相应的AGP受体。我们发现，AGP引起的[Ca 2 +] i在Fura-2负载中性粒细胞的最小上升，这种反应显着增强预处理抗L-选择素抗体。(The AGP诱导的Ca ~（2+）应答的EC_（50）值为9 μ g/ml。磷脂酶-C、Src酪氨酸激酶和PI 3激酶的激活被证明是AGP介导的[Ca 2 +] i增加所必需的，而p38 MAPK和SYK信号通路不参与。此外，针对唾液酸结合、免疫球蛋白样凝集素5（Siglec-5）和寡糖3 '-唾液酸-乳糖的抗体均拮抗AGP诱导的应答，并引起抗L-选择素处理的嗜中性粒细胞中[Ca 2 +] i的立即增加，这表明Siglec-5的信号传导能力。我们使用改良形式的AGP（用温和的高碘酸盐或神经氨酸酶处理）来确定唾液酸残基的重要性。改良形式的AGP引起的[Ca 2 +] i的上升比未改变的AGP小得多。亲和色谱法证实，未改变的AGP而非神经氨酸酶处理的AGP结合Siglec-5。我们的报告提供了第一个证据表明，通过一个明确的受体的信号转导能力的AGP。预接合的L-选择素显着增强了这种信号转导能力。-Gunnarsson，P.，莱万德湖，Pahlsson，P.，格雷萨尔，M.急性时相蛋白α（1）-酸性糖蛋白（AGP）通过唾液酸结合免疫球蛋白样凝集素（Siglecs）诱导中性粒细胞中胞质Ca 2+的升高。
We studied whether the acute-phase protein alpha(1)-acid glycoprotein (AGP) induces rises in [Ca2+](i) in neutrophils and sought to identify the corresponding AGP receptor (or receptors). We found that AGP elicited a minimal rise in [Ca2+] i in Fura-2-loaded neutrophils, and this response was markedly enhanced by pretreatment with anti-L-selectin antibodies. (The EC50 value of the AGP-induced Ca2+ response was 9 mu g/ml.) Activation of phospholipase-C, Src tyrosine kinases, and PI3 kinases proved to be essential for the AGP-mediated increase in [Ca2+] i, whereas the p38 MAPK and SYK signaling pathways were not involved. Furthermore, antibodies against sialic acid binding, immunoglobulin-like lectin 5 (Siglec-5) and oligosaccharide 3 '- sialyl-lactose both antagonized the AGP-induced response and caused an immediate increase in [Ca2+] i in anti-L-selectin-treated neutrophils, which indicates a signaling capacity of Siglec-5. We used modified forms of AGP (treated with mild periodate or neuraminidase) to establish the importance of sialic acid residues. The modified forms of AGP caused a much smaller rise in [Ca2+] i than did unaltered AGP. Affinity chromatography confirmed that unchanged AGP, but not neuraminidase-treated AGP, bound to Siglec-5. Our report provides the first evidence for a signaling capacity by AGP through a defined receptor. Pre-engagement of L-selectin significantly enhanced this signaling capacity. -Gunnarsson, P., Levander, L., Pahlsson, P., Grenegard, M. The acute- phase protein alpha(1)- acid glycoprotein (AGP) induces rises in cytosolic Ca2+ in neutrophil granulocytes via sialic acid binding immunoglobulin- like lectins (Siglecs).