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Macrophages programmed by apoptotic cells promote angiogenesis via prostaglandin E 2
Author(s) -
Brecht Kerstin,
Weigert Andreas,
Hu Jiong,
Popp Rüdiger,
Fisslthaler Beate,
Korff Thomas,
Fleming Ingrid,
Geisslinger Gerd,
Brüne Bernhard
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-179473
Subject(s) - angiogenesis , microbiology and biotechnology , matrigel , chemistry , prostaglandin , apoptosis , prostaglandin e2 , lipid signaling , prostaglandin e2 receptor , macrophage , prostaglandin e , inflammation , cancer research , biology , immunology , in vitro , receptor , endocrinology , biochemistry , agonist
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 upregulate 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., Brüne, B. Macrophages programmed by apoptotic cells promote angiogenesis via prostaglandin E 2 . FASEB J. 25, 2408–2417 (2011). www.fasebj.org