Phagocytosis of Apoptotic Cells in Resolution of Inflammation.

Ioannis Kourtzelis,George Hajishengallis,Triantafyllos Chavakis

doi:10.3389/fimmu.2020.00553

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.

Highlights

Phagocytosis of Apoptotic Cells in Resolution of InflammationEfficient inflammation resolution is important for the termination of the inflammatory response and for the restoration of tissue integrity
Alterations in cellular metabolism are critical for shaping the phenotype and function of efferocytic macrophages, representing an important determinant of macrophage plasticity
Macrophage efferocytosis is a major player in resolution of inflammation

Summary

Phagocytosis of Apoptotic Cells in Resolution of Inflammation

Efficient inflammation resolution is important for the termination of the inflammatory response and 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. The endothelial cell-derived molecule promotes anti-inflammatory activity by blocking β2 integrindependent leukocyte recruitment, whereas DEL-1 derived from macrophages promotes efferocytosis-dependent resolution of inflammation [33, 41] (Figure 1). Platelet and endothelial cell adhesion molecule 1 (PECAM-1, CD31) exerts a “don’t eat-me” function In this regard, homotypic CD31 interaction between non-apoptotic neutrophils and macrophages may prevent phagocytic clearance [62]. Activation of IFN-β signaling via STAT3 enhances apoptosis of neutrophils and their subsequent efferocytic clearance, resulting in a pro-resolving reprograming of macrophages [79]

METABOLIC MODULATION OF MACROPHAGE FUNCTION IN THE CONTEXT OF EFFEROCYTOSIS

CONCLUDING REMARKS