Macrophages programmed by apoptotic cells promote angiogenesis via prostaglandin E2
Macrophages programmed by apoptotic cells promote angiogenesis via prostaglandin E2
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DOI：
10.1096/fj.10-179473
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发表时间：
2011-07-01
期刊：
影响因子：
4.8
通讯作者：
Bruene, Bernhard
中科院分区：
文献类型：
--
作者：
Brecht, Kerstin;Weigert, Andreas;Bruene, Bernhard
巨噬细胞有助于组织稳态在发展和成年生物体。它们促进损伤后的组织再生和重塑，这需要有效的新生血管生成。激活巨噬细胞血管生成程序的信号通路仍然不明确。我们报道了来自应激或受损组织的凋亡细胞（ACs）可以诱导原代人巨噬细胞的血管生成特性。来自ACs的信号是脂质介质鞘氨醇-1-磷酸（S1P），它激活巨噬细胞上的S1P1/3上调环氧化酶-2。前列腺素E-2 （PGE(2)）的形成和释放刺激内皮细胞的迁移。这是通过在体外使用PGE(2)受体拮抗剂或中和PGE(2)抗体来证明的，从而通过Boyden室试验减弱内皮细胞的迁移。在体内，从促血管生成的巨噬细胞上清液中中和的PGE(2)阻断了血管形成成Matrigel塞。特别是，凋亡的癌细胞通过上调环氧化酶-2和微粒体前列腺素E合成酶-1 (mPGES1)，下调PGE(2)降解酶15-羟基前列腺素脱氢酶（15-PGDH）或前列腺素d合成酶（PGDS），使巨噬细胞中的前列腺素形成选择性地转向PGE(2)。因此，ACs对巨噬细胞的血管生成编程可能控制对组织应激的反应，例如在肿瘤中，巨噬细胞支持癌症进展。-Brecht， K., Weigert， A., Hu， J., Popp， R., Fisslthaler， B., Korff， T., Fleming， I., Geisslinger， G., Brune， B.凋亡细胞编程的巨噬细胞通过前列腺素E-2促进血管生成。中国生物医学工程学报，25(4):444 - 444（2011）。www.fasebj.org
Macrophages contribute to tissue homeostasis in the developing as well as the adult organism. They promote tissue regeneration and remodeling after injury, which requires efficient neoangiogenesis. Signaling pathways activating an angiogenic program in macrophages are still poorly defined. We report that apoptotic cells (ACs), which originate from stressed or damaged tissues, can induce angiogenic properties in primary human macrophages. The signal originating from ACs is the lipid mediator sphingosine-1-phosphate (S1P), which activates S1P1/3 on macrophages to up-regulate cyclooxygenase-2. The formation and liberation of prostaglandin E-2 (PGE(2)) then stimulates migration of endothelial cells. This is demonstrated by using PGE(2) receptor antagonists or a neutralizing PGE(2) antibody in vitro, thereby attenuating endothelial cell migration using a Boyden chamber assay. In vivo, neutralization of PGE(2) from proangiogenic macrophage supernatants blocked vessel formation into Matrigel plugs. In particular, apoptotic cancer cells shifted prostanoid formation in macrophages selectively toward PGE(2) by up-regulating cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (mPGES1), while down-regulating the PGE(2)-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) or prostaglandin-D synthase (PGDS). Angiogenic programming of macrophages by ACs, therefore, may control responses to tissue stress such as in tumors, where macrophages support cancer progression.-Brecht, K., Weigert, A., Hu, J., Popp, R., Fisslthaler, B., Korff, T., Fleming, I., Geisslinger, G., Brune, B. Macrophages programmed by apoptotic cells promote angiogenesis via prostaglandin E-2. FASEB J. 25, 2408-2417 (2011). www.fasebj.org