Receptor for advanced glycation end products binds to phosphatidylserine and assists in the clearance of apoptotic cells

He, Mei; Kubo, Hiroshi; Morimoto, Konosuke; Fujino, Naoya; Suzuki, Takaya; Takahasi, Toru; Yamada, Mitsuhiro; Yamaya, Mutsuo; Maekawa, Takuji; Yamamoto, Yasuhiko; Yamamoto, Hiroshi

doi:10.1038/embor.2011.28

Cited by 196 publications

(159 citation statements)

References 32 publications

(34 reference statements)

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“…Exposed phosphatidylserine is recognized by macrophages and dendritic cells, which have receptors that recognize phosphatidylserine directly through TIM 3 and TIM 4, brain-specific angiogenesis inhibitor 1 (BAI1), stabilin-2, or receptor for advanced glycation end-products (RAGE; refs. [29][30][31][32], or indirectly through a variety of bridging proteins (33,34). Binding to macrophage phosphatidylserine receptors triggers IL-10-and TGF-b-dependent immunosuppressive signals that stimulate them to engulf the phosphatidylserine-expressing cells without secreting inflammatory cytokines (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation

Yin

Huang

Lynn

et al. 2013

Cancer Immunology Research

124

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Multiple tumor-derived factors are responsible for the accumulation and expansion of immune-suppressing myeloid-derived suppressor cells (MDSC) and M2-like tumor-associated macrophages (TAM) in tumors. Here, we show that treatment of tumor-bearing mice with docetaxel in combination with the phosphatidylserine-targeting antibody 2aG4 potently suppressed the growth and progression of prostate tumors, depleted M2-like TAMs, and MDSCs, and increased the presence of M1-like TAMs and mature dendritic cells in the tumors. In addition, the antibody markedly altered the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. In vitro studies confirmed that 2aG4 repolarized TAMs from an M2-to an M1-like phenotype and drove the differentiation of MDSCs into M1-like TAMs and functional dendritic cells. These data suggest that phosphatidylserine is responsible for the expansion of MDSCs and M2-like TAMs in tumors, and that bavituximab, a phosphatidylserine-targeting antibody currently in clinical trials for cancer, could reverse this process and reactivate antitumor immunity. Cancer Immunol Res; 1(4); 256-68. Ó2013 AACR.

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Section: Introductionmentioning

confidence: 99%

Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation

Yin

Huang

Lynn

et al. 2013

Cancer Immunology Research

124

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“…RAGE ligands include advanced glycation end products (AGEs), high mobility group box chromosomal protein 1 (HMGB1), lipopolysaccharide (LPS), macrophage-1 antigen (Mac-1), phosphatidylserine and S100/calgranulin and under pathologic conditions activate microglia [42][43][44][45][46], which then secrete and synthesize RAGE ligands, such as, AGEs, HMGB1 and S100β in AD [29] ( Figure 2) and PD [47].…”

Section: Secretion and Synthesis Of Rage Ligands By Activated Microglmentioning

confidence: 99%

Ligands of Receptor for Advanced Glycation End-Products Produced by Activated Microglia are Critical in Neurodegenerative Diseases

Son¹,

Oh²,

Lee³

et al. 2017

J Alzheimers Dis Parkinsonism

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“…Once the PtdSer (Phosphatidylserine) is displayed on cell surface, it gets directly bound by any of the phagocytic cell surface receptor such as PSR (Phosphatidylserine receptor), BAI1 (Brain specific angiogenesis inhibitor 1), Stabilin-2 (also known as hyaluronic acid receptor for endocytosis or HARE), RAGE (receptor for advanced glycation end product) [54,55]. The bonding between the/PtdSer and its cognate receptor activates signaling cascade employing CRKIII-DOCK180-ELMO.…”

Section: Immurement Of Immunogenic Cancermentioning

confidence: 99%

Masking Anti-Phagocytic Signal of Tumor by Pro-Phagocytic Signal-a Key to Immurement of Cancer Cell

Mickymaray

Gurusamy

Natarajan

2016

Int J Pharm Pharm Sci

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Immune surveillance is a mechanism where cells and tissues are watched constantly by ever alerted immune system. Most incipient cancer cells are recognized and eliminated by the immune surveillance mechanism, but still tumors have the ability to evade immune surveillance and immunological killing. One greater arm that tumor use to evade immune surveillance, is by expressing anti-phagocytic signal (CD47). Here we present a provocative hypothesis where cancer cells are removed alive by phagocytic cell (DC). That in turn will elicit effective and higher immunogenic condition. All this could be possible by addition pro-phagocytic signal (PtdSer) over cancer cell surface (Breast Cancer), that mask the presence of anti-phagocytic signal (CD47). In other words, adding eat me signal (PtdSer) over the breast cancer cell surface that mask the presence of don't eat me signal or anti-phagocytic signal present in breast cancer cell surface. This could be possible by using bi-specific antibody, conjugated to PEG-modified liposomes, which carry (PtdSer) pro-phagocytic signal (or) eat me signal, which target both CD47 and EGFRVIII on breast carcinoma. The simultaneous masking of anti-phagocytic signal, and adding of pro-phagocytic signal over cancer cell, will enhance the phagocytic clearance of live tumor cell and elicit immunological killing.

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Receptor for advanced glycation end products binds to phosphatidylserine and assists in the clearance of apoptotic cells

Cited by 196 publications

References 32 publications

Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation

Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation

Ligands of Receptor for Advanced Glycation End-Products Produced by Activated Microglia are Critical in Neurodegenerative Diseases

Masking Anti-Phagocytic Signal of Tumor by Pro-Phagocytic Signal-a Key to Immurement of Cancer Cell

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