Effect of soluble cleavage products of important receptors/ligands on efferocytosis: Their role in inflammatory, autoimmune and cardiovascular disease

Tajbakhsh, Amir; Hayat, Seyed Mohammad Gheibi; Butler, Alexandra E.; Sahebkar, Amirhossein

doi:10.1016/j.arr.2019.01.007

Cited by 39 publications

(31 citation statements)

References 194 publications

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“…In physiological conditions, as efferocytosis occurs efficiently and swiftly, it is hard to find free apoptotic corpses throughout body tissues, even when large numbers of cells undergo apoptosis. Such effective clearance of cells that are no longer desired or are functionally abnormal is crucial for the maintenance of tissue homeostasis and for the prevention of various diseases including cancer [22,23], degenerative diseases of the central nervous system, atherosclerosis and autoimmune diseases [24][25][26][27][28]. Therefore, efferocytosis mediators may represent potential therapeutic targets for either the prevention or the treatment of these pathological conditions [29][30][31].…”

Section: Exposure Of Ps: Apoptotic and Non-apoptotic Rolementioning

confidence: 99%

The role of phosphatidylserine recognition receptors in multiple biological functions

et al. 2020

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Apoptotic cells are rapidly engulfed and degraded by phagocytes through efferocytosis. Efferocytosis is a highly regulated process. It is triggered upon the activation of caspase-dependent apoptosis, which in turn promotes the expression of "eat me" signals on the surface of dying cells and the release of soluble "find me" signals for the recruitment of phagocytes. To date, many "eat me" signals have been recognized, including phosphatidylserine (PS), intercellular adhesion molecule-3, carbohydrates (e.g., amino sugars, mannose) and calreticulin. Among them, PS is the most studied one. PS recognition receptors are different functionally active receptors expressed by phagocytes. Various PS recognition receptors with different structure, cell type expression, and ability to bind to PS have been recognized. Although PS recognition receptors do not fall into a single classification or family of proteins due to their structural differences, they all share the common ability to activate downstream signaling pathways leading to the production of anti-inflammatory mediators. In this review, available evidence regarding molecular mechanisms underlying PS recognition receptor-regulated clearance of apoptotic cells is discussed. In addition, some efferocytosis-independent biological functions of PS recognition receptors are reviewed.

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Section: Exposure Of Ps: Apoptotic and Non-apoptotic Rolementioning

confidence: 99%

The role of phosphatidylserine recognition receptors in multiple biological functions

et al. 2020

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“…Indeed, apoptotic cell receptors and bridging molecules related to the recognition and engulfment have been found to be defective in SLE. Tyro-3, Axl, and Mer (TAM) receptor protein tyrosine kinases are important receptors on phagocytes for the clearance of apoptotic cells by their recognition of ligands that are bound to PS exposed on the membrane of apoptotic cells [30, 31]. Mer-deficient mice displayed accumulation of apoptotic and secondary necrotic cells in peripheral tissues and developed SLE-like autoimmunity [32].…”

Section: Apoptosis and Secondary Necrosis After Apoptosismentioning

confidence: 99%

Programmed Cell Death Pathways in the Pathogenesis of Systemic Lupus Erythematosus

Yang

Zhai

et al. 2019

Journal of Immunology Research

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Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by excessive inflammatory and immune responses and tissue damage. Increasing evidence has demonstrated the important role of programmed cell death in SLE pathogenesis. When apoptosis encounters with defective clearance, accumulated apoptotic cells lead to secondary necrosis. Different forms of lytic cell death, including secondary necrosis after apoptosis, NETosis, necroptosis, and pyroptosis, contribute to the release of damage-associated molecular patterns (DAMPs) and autoantigens, resulting in triggering immunity and tissue damage in SLE. However, the role of autophagy in SLE pathogenesis is in dispute. This review briefly discusses different forms of programmed cell death pathways and lay particular emphasis on inflammatory cell death pathways such as NETosis, pyroptosis, and necroptosis and their roles in the inflammatory and immune responses in SLE.

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“…A generally accepted definition of efferocytosis is the clearance of apoptotic cells (ACs) by professional or nonprofessional phagocytic cells [13][14][15][16]. A large and ever-growing body of literature has demonstrated that the most important steps in the formation of atherosclerotic plaques are the accumulation of inflammatory cells (viz.…”

Section: Introductionmentioning

confidence: 99%

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

Tajbakhsh

Kovanen

Rezaee

et al. 2019

JCM

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In atherosclerosis, macrophages in the arterial wall ingest plasma lipoprotein-derived lipids and become lipid-filled foam cells with a limited lifespan. Thus, efficient removal of apoptotic foam cells by efferocytic macrophages is vital to preventing the dying foam cells from forming a large necrotic lipid core, which, otherwise, would render the atherosclerotic plaque vulnerable to rupture and would cause clinical complications. Ca 2+ plays a role in macrophage migration, survival, and foam cell generation. Importantly, in efferocytic macrophages, Ca 2+ induces actin polymerization, thereby promoting the formation of a phagocytic cup necessary for efferocytosis. Moreover, in the efferocytic macrophages, Ca 2+ enhances the secretion of anti-inflammatory cytokines. Various Ca 2+ antagonists have been seminal for the demonstration of the role of Ca 2+ in the multiple steps of efferocytosis by macrophages. Moreover, in vitro and in vivo experiments and clinical investigations have revealed the capability of Ca 2+ antagonists in attenuating the development of atherosclerotic plaques by interfering with the deposition of lipids in macrophages and by reducing plaque calcification. However, the regulation of cellular Ca 2+ fluxes in the processes of efferocytic clearance of apoptotic foam cells and in the extracellular calcification in atherosclerosis remains unknown. Here, we attempted to unravel the molecular links between Ca 2+ and efferocytosis in atherosclerosis and to evaluate cellular Ca 2+ fluxes as potential treatment targets in atherosclerotic cardiovascular diseases.

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Effect of soluble cleavage products of important receptors/ligands on efferocytosis: Their role in inflammatory, autoimmune and cardiovascular disease

Cited by 39 publications

References 194 publications

The role of phosphatidylserine recognition receptors in multiple biological functions

The role of phosphatidylserine recognition receptors in multiple biological functions

Programmed Cell Death Pathways in the Pathogenesis of Systemic Lupus Erythematosus

Ca2+ Flux: Searching for a Role in Efferocytosis of Apoptotic Cells in Atherosclerosis

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