Phagocytosis of Apoptotic Cells in Resolution of Inflammation

Abstract

Efficient inflammation resolution is important not only for the termination of the inflammatory response but also for the restoration of tissue integrity. An integral process to resolution of inflammation is the phagocytosis of dying cells by macrophages, known as efferocytosis. This function is mediated by a complex and well-orchestrated network of interactions amongst specialized phagocytic receptors, bridging molecules, as well as "find-me" and "eat-me" signals. Efferocytosis serves not only as a waste disposal mechanism (clearance of the apoptotic cells) but also promotes a pro-resolving phenotype in efferocytic macrophages and thereby termination of inflammation. Alterations in cellular metabolism are critical for shaping the phenotype and function of efferocytic macrophages, thus, representing an important determinant of macrophage plasticity. Impaired efferocytosis can result in inflammation-associated pathologies or autoimmunity. The present mini review summarizes current knowledge regarding the mechanisms regulating macrophage efferocytosis during clearance of inflammation.

Analysis of the Immune Response to Sciatic Nerve Injury Identifies Efferocytosis as a Key Mechanism of Nerve Debridement

“…After a short pro-inflammatory phase, the immune milieu rapidly transitions toward resolution and is dominated (Yoon et al, 2015). In the injured sciatic nerve, Tgfb1 is expressed by myeloid cells and is important for axon regeneration (Clements et al, 2017;Kourtzelis et al, 2020).…”

“…Conversely, healthy cells display the "don't eat me" signal CD47 that binds to the cell surface receptor SIRPα (signal regulatory protein α ) encoded by Sirpa, to block efferocytosis (Kourtzelis et al, 2020). advantage of recently published scRNA-seq data sets generated from naïve mouse sciatic nerve tissue (Wang et al, 2020;Ydens et al, 2020).…”

Sex-dependent differences in the secretome of human endothelial cells

“…Our ndings, showing that the silencing of PTX3 impaired efferocytosis only in male ECs, but not in female, suggest that this protein might act as an endothelial eat-me-signal in a sex-dependent manner. At variance with other forms of cell death, apoptosis is a nonin ammatory process, and the timely phagocytosis of dying cells by macrophages prevents the release of in ammatory factors, the establishing of in ammation, and the development of chronic in ammatory disorders, such as atherosclerosis [38,39,60]. Therefore, the involvement of PTX3 in the resolution of the male apoptotic process may re ect the effort of secreted PTX3 to maintain vascular integrity and to counteract chronic endothelial in ammation via the prompt execution of the efferocytotic process.…”

Galectin-3 in Inflammasome Activation and Primary Biliary Cholangitis Development

“…Regardless of the fact that this autoantigen is ubiquitous, the targeted damage of cholangiocytes is probably a consequence of aberrant modification of mitochondrial PDC-E2, keeping intact the immunodominant epitope, within the apoptotic bodies of biliary epithelial cells. This immunogenic complex is recognized by circulating antibodies resulting in the formation of antigen–antibody complexes [ 31 , 32 ]. Increased levels of AMA in the serum and infiltration of the liver and portal spaces of PBC patients with CD4+ T and CD8+ T lymphocytes indicate the role of a specific immune response in PBC pathogenesis [ 33 , 34 ].…”