Stabilin Receptors: Role as Phosphatidylserine Receptors

Park, Seung Yoon; Kim, In San

doi:10.3390/biom9080387

Cited by 15 publications

(15 citation statements)

References 119 publications

(143 reference statements)

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“…Here, we briefly introduce the most studied PS receptors and their expression on immune cells. For more details on each PS receptor, please see other published reviews 89 - 92 .…”

Section: Ps Biologymentioning

confidence: 99%

“…Stabilin-1 and stabilin-2 are widely expressed in endothelial cells in different organs, such as the liver, spleen, lymph nodes, bone marrow (stabilin-2), and adrenal cortex (stabilin-1) 92 , 93 . In apoptotic cells, stabilin-1 and stabilin-2 directly bind to PS on the cell surface and initiate cell engulfment by activation of Rac family small GTPase 1 (Rac1) via a phosphotyrosine-binding domain-containing engulfment adaptor protein (Gulp1)-dependent mechanism or a Gulp1-independent pathway 92 . On immune cells, stabilin-1 is expressed in alternatively activated macrophages, also known as M2-like macrophages.…”

Section: Ps Biologymentioning

confidence: 99%

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Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Chang

Xiao

et al. 2020

Theranostics

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Cancer is a leading cause of mortality and morbidity worldwide. Despite major improvements in current therapeutic methods, ideal therapeutic strategies for improved tumor elimination are still lacking. Recently, immunotherapy has attracted much attention, and many immune-active agents have been approved for clinical use alone or in combination with other cancer drugs. However, some patients have a poor response to these agents. New agents and strategies are needed to overcome such deficiencies. Phosphatidylserine (PS) is an essential component of bilayer cell membranes and is normally present in the inner leaflet. In the physiological state, PS exposure on the external leaflet not only acts as an engulfment signal for phagocytosis in apoptotic cells but also participates in blood coagulation, myoblast fusion and immune regulation in nonapoptotic cells. In the tumor microenvironment, PS exposure is significantly increased on the surface of tumor cells or tumor cell-derived microvesicles, which have innate immunosuppressive properties and facilitate tumor growth and metastasis. To date, agents targeting PS have been developed, some of which are under investigation in clinical trials as combination drugs for various cancers. However, controversial results are emerging in laboratory research as well as in clinical trials, and the efficiency of PS-targeting agents remains uncertain. In this review, we summarize recent progress in our understanding of the physiological and pathological roles of PS, with a focus on immune suppressive features. In addition, we discuss current drug developments that are based on PS-targeting strategies in both experimental and clinical studies. We hope to provide a future research direction for the development of new agents for cancer therapy.

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“…Here, we briefly introduce the most studied PS receptors and their expression on immune cells. For more details on each PS receptor, please see other published reviews 89 - 92 .…”

Section: Ps Biologymentioning

confidence: 99%

Section: Ps Biologymentioning

confidence: 99%

Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Chang

Xiao

et al. 2020

Theranostics

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“…With binding sites that interact with cells throughout the larger Stab2 receptor, it is easier to envision more efficient phagocytosis mediated by Stab2 than could occur with HARE, with half the number of binding sites for ligands on macro-scale ligands. In this special issue, Park and Kim [59] summarize our current understanding of how the full-length Stab1 and Stab2 proteins function as PS receptors to mediate the critical function of phagocytosis.…”

Section: A Stress Sensor Model For Hyaluroan Receptor For Endocytmentioning

confidence: 99%

Discovery of the Liver Hyaluronan Receptor for Endocytosis (HARE) and Its Progressive Emergence as the Multi-Ligand Scavenger Receptor Stabilin-2

Weigel

2019

Biomolecules

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Since the discovery of a novel liver hyaluronan (HA) clearance receptor in 1981 by Laurent, Fraser and coworkers, 22 different ligands cleared by the renamed receptor (the Hyaluronan Receptor for Endocytosis (HARE); Stabilin-2 (Stab2)) were discovered over 37 years. Ligands fall into three groups: (1) 11 anionic polymers, (2) seven cleaved or modified proteins and (3) four types of cells. Seven synthetic ligands, not found normally in serum or tissues, likely mimic natural molecules cleared by the receptor. In 2002 we purified and cloned HARE, based on HA-binding activity, and two other groups cloned full-length receptor; FEEL-2 and Stab2. Macrophages likely require full-length Stab2 for efficient binding and phagocytosis of bacteria or apoptotic cells, since cell-binding domains are throughout the receptor. In contrast, all 16 known single-molecule binding sites are only within the C-terminal half (190HARE). The HARE isoform is generated by proteolysis, not mRNA splicing. The majority of circulating ligands is cleared by HARE, since sinusoidal endothelial cells of liver, spleen and lymph node express twice as many HARE half-receptors as full-length receptors. Based on their significant binding and functional differences, a modified receptor nomenclature is proposed that designates HARE as the C-terminal half-receptor isoform and Stab2 as the full-length receptor isoform.

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“…Once exposed, PtdSer is recognized by many receptors expressed by efferocytes ( Figure 1 B). Receptors that bind directly to PtdSer include members of the T cell immunoglobulin mucin (TIM) receptor family such as TIM-1, TIM-3, and TIM-4 [ 80 ], brain angiogenesis inhibitor 1 (BAI1) [ 81 ], stabilin 2 [ 82 ], members of the CD300 family [ 83 ], and the receptor for advanced glycation end products (RAGE) [ 84 ]. Other efferocytic receptors indirectly recognize PtdSer via soluble opsonins such as sCD93 [ 85 ], MFG-E8 [ 86 ], CCN1 [ 87 ], GAS6 [ 88 ], and Protein S [ 88 ].…”

Section: Mechanisms Of Efferocytosismentioning

confidence: 99%

“…Efferocytic receptors which use the CrkII-ELMO-Dock180 Rac1-activating pathway include integrin α v β 3/5 , MERTK, and BAI1 [ 81 , 108 , 109 ]. Activation of Rac1 by the ELMO1/DOCK180 complex reorganizes the cortical actin cytoskeleton through Arp2/3 induced actin polymerization [ 82 , 105 , 107 ]. This polymerization drives extensions of the plasma membrane around the apoptotic cell, first forming a cup-like structure, which over time completely envelops the apoptotic cell.…”

Section: Mechanisms Of Efferocytosismentioning

confidence: 99%

Role of Apoptotic Cell Clearance in Pneumonia and Inflammatory Lung Disease

2021

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Pneumonia and inflammatory diseases of the pulmonary system such as chronic obstructive pulmonary disease and asthma continue to cause significant morbidity and mortality globally. While the etiology of these diseases is highly different, they share a number of similarities in the underlying inflammatory processes driving disease pathology. Multiple recent studies have identified failures in efferocytosis—the phagocytic clearance of apoptotic cells—as a common driver of inflammation and tissue destruction in these diseases. Effective efferocytosis has been shown to be important for resolving inflammatory diseases of the lung and the subsequent restoration of normal lung function, while many pneumonia-causing pathogens manipulate the efferocytic system to enhance their growth and avoid immunity. Moreover, some treatments used to manage these patients, such as inhaled corticosteroids for chronic obstructive pulmonary disease and the prevalent use of statins for cardiovascular disease, have been found to beneficially alter efferocytic activity in these patients. In this review, we provide an overview of the efferocytic process and its role in the pathophysiology and resolution of pneumonia and other inflammatory diseases of the lungs, and discuss the utility of existing and emerging therapies for modulating efferocytosis as potential treatments for these diseases.

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Stabilin Receptors: Role as Phosphatidylserine Receptors

Cited by 15 publications

References 119 publications

Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Targeting phosphatidylserine for Cancer therapy: prospects and challenges

Discovery of the Liver Hyaluronan Receptor for Endocytosis (HARE) and Its Progressive Emergence as the Multi-Ligand Scavenger Receptor Stabilin-2

Role of Apoptotic Cell Clearance in Pneumonia and Inflammatory Lung Disease

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