Participation of the receptor for advanced glycation end products in efferocytosis.

Participation of the receptor for advanced glycation end products in efferocytosis.
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DOI:
10.4049/jimmunol.1004134
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发表时间:
2011-06-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Abraham E
Abraham E
中科院分区:
其他
文献类型:
--
作者:
Friggeri A;Banerjee S;Biswas S;de Freitas A;Liu G;Bierhaus A;Abraham E

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巨噬细胞和其他吞噬细胞清除凋亡细胞,称为efferocytosis,是炎症消退的核心过程。虽然晚期糖基化终产物受体(RAGE)已被证明参与肺和其他器官的各种急性和慢性炎症过程,但RAGE在efferocytosis中的作用尚未报道。在目前的研究中,我们研究了RAGE在efferocytosis中的潜在参与。转基因RAGE - / -小鼠巨噬细胞吞噬凋亡中性粒细胞和胸腺细胞的能力下降。RAGE+/+巨噬细胞的晚期糖基化终产物(与RAGE竞争性结合)或抗RAGE的抗体预处理可减少凋亡细胞的吞噬作用。RAGE在人胚胎肾293细胞中的过表达导致吞噬凋亡细胞的能力增强。此外,我们发现与可溶性RAGE孵育可以增强RAGE+/+和RAGE - / -巨噬细胞对凋亡细胞的吞噬作用。固相ELISA法证实RAGE可直接与凋亡细胞上高表达的“吃我”信号磷脂酰丝氨酸(PS)结合。在粘附实验中证实了RAGE与凋亡细胞上的PS结合的能力。在体内条件下,RAGE - / -小鼠的肺和腹腔中发现巨噬细胞对凋亡中性粒细胞的摄取减少。这些结果证明了RAGE的一个新作用,它能够通过与凋亡细胞上的PS结合来增强efferocytosis。
Clearance of apoptotic cells by macrophages and other phagocytic cells, called efferocytosis, is a central process in the resolution of inflammation. Although the receptor for advanced glycation end products (RAGE) has been shown to participate in a variety of acute and chronic inflammatory processes in the lungs and other organs, a role for RAGE in efferocytosis has not been reported. In the present studies, we examined the potential involvement of RAGE in efferocytosis. Macrophages from transgenic RAGE−/− mice showed a decreased ability to engulf apoptotic neutrophils and thymocytes. Pretreatment of RAGE+/+ macrophages with advanced glycation end products, which competitively bind to RAGE, or Abs against RAGE diminished phagocytosis of apoptotic cells. Overexpression of RAGE in human embryonic kidney 293 cells resulted in an increased ability to engulf apoptotic cells. Furthermore, we found that incubation with soluble RAGE enhances phagocytosis of apoptotic cells by both RAGE+/+ and RAGE−/− macrophages. Direct binding of RAGE to phosphatidylserine (PS), an “eat me” signal highly expressed on apoptotic cells, was shown by using solid-phase ELISA. The ability of RAGE to bind to PS on apoptotic cells was confirmed in an adhesion assay. Decreased uptake of apoptotic neutrophils by macrophages was found under in vivo conditions in the lungs and peritoneal cavity of RAGE−/− mice. These results demonstrate a novel role for RAGE in which it is able to enhance efferocytosis through binding to PS on apoptotic cells.
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