Effect of diabetes on efferocytosis process

Immunology of chronic low-grade inflammation: relationship with metabolic function

“…The classically activated macrophages are phagocytic/ cytotoxic and have a high glycolytic rate (Jha et al 2015, Rasheed & Rayner 2021. These cells assist with the clearing of tissue debris (apoptotic bodies) and play a crucial role in recognizing apoptotic neutrophils and removing dead cells through the process of efferocytosis (Mahmoudi et al 2022). This process is reviewed elsewhere but involves (i) recognition of dead/dying cells through 'find me' signals, which include soluble chemokines, nucleotides, and membrane lipids; (ii) phagocytic macrophages respond to 'eat me' signals such as a lack of phospholipid asymmetry on the plasma membrane, display of endoplasmic reticulum lumen proteins on the cell surface and the presence of lipid biomolecules (lysophosphatidylcholine, LPC) on apoptotic bodies; and iii) engulfs/destroys the apoptotic cell to recycle cellular components and restore homeostasis (Mahmoudi et al 2022, Tajbakhsh et al 2022.…”

“…During this process, lysosomal degradation of apoptotic bodies through catabolism of cell corpses furthermore provides substrates for the metabolic switch to favour oxidative phosphorylation and triggers various nuclear transcription factors to induce the transcription of immunosuppressive cytokines such as IL10 and transforming growth factor-β (Zhang et al 2019b). Disruption of efferocytosis as seen in metabolic disorders, such as diabetes, results in the accumulation of necrotic/pyroptotic neutrophil bodies which aggravate inflammation through increased activation of M1 macrophages, dendritic cells, and Th1/Th17 lymphocyte responses (Lee et al 2022, Mahmoudi et al 2022. In addition to continuous activation signals observed in obesity and diabetes, given the importance of intracellular metabolism in determining macrophage function, aberrant activation and reprogramming of macrophages also occur due to metabolic disturbances (An et al 2019, Mahmoudi et al 2022.…”

“…Disruption of efferocytosis as seen in metabolic disorders, such as diabetes, results in the accumulation of necrotic/pyroptotic neutrophil bodies which aggravate inflammation through increased activation of M1 macrophages, dendritic cells, and Th1/Th17 lymphocyte responses (Lee et al 2022, Mahmoudi et al 2022. In addition to continuous activation signals observed in obesity and diabetes, given the importance of intracellular metabolism in determining macrophage function, aberrant activation and reprogramming of macrophages also occur due to metabolic disturbances (An et al 2019, Mahmoudi et al 2022. There is however currently a lack of pharmaceutical agents to target the mitochondrial metabolism of macrophages to promote the resolution of inflammation.…”

Dipotassium glycyrrhizate and hinokitiol enhance macrophage efferocytosis by regulating recognition, uptake, and metabolism of apoptotic cells in vitro

“…Defective efferocytosis is associated with increased age and various chronic inflammatory diseases such as atherosclerosis, systemic lupus erythematosus, obesity, and diabetes. [3][4][5][6][7] In periodontal disease, impaired efferocytosis leads to the progression of pathological conditions such as alveolar bone destruction, suggesting that efferocytosis plays an important role in periodontal tissue protection. 8,9 Apoptotic cell clearance consists of three major steps: recognition, uptake, and metabolism.…”

“…The clearance of apoptotic neutrophils by phagocytes, such as macrophages, a process referred to as efferocytosis, plays a key role in maintaining tissue homeostasis. Defective efferocytosis is associated with increased age and various chronic inflammatory diseases such as atherosclerosis, systemic lupus erythematosus, obesity, and diabetes 3–7 . In periodontal disease, impaired efferocytosis leads to the progression of pathological conditions such as alveolar bone destruction, suggesting that efferocytosis plays an important role in periodontal tissue protection 8,9 …”