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Potential of Herbal Extracts and Bioactive Compounds for Human Healthcare
Published in Megh R. Goyal, Hafiz Ansar Rasul Suleria, Ramasamy Harikrishnan, The Role of Phytoconstitutents in Health Care, 2020
Ramasamy Harikrishnan, Chellam Balasundaram
The phagocytic cells are eliminated of dead cells in an orderly fashion without elicit any inflammatory process known as efferocytosis, which marks the terminal stage of apoptosis [498] and display phosphatidylserine on phagocytic cell surface [558]. The phosphatidylserine normally found on the inner leaflet surface of the plasma membrane and redistributed during apoptosis to the extracellular surface by a protein known as scram-blase [1017]. These molecules imprint the cell for phagocytosis through appropriate receptors, such as macrophages [840]. During the apoptosis, the cellular RNA and DNA are disassociated from each other into various apoptotic bodies [327].
Chronic obstructive pulmonary disease
Published in Louis-Philippe Boulet, Applied Respiratory Pathophysiology, 2017
Julie Milot, Mathieu Morissette
Efferocytosis refers to a phenomenon by which cells of the immune system, mainly phagocytes, eliminate apoptotic cells. This apoptotic cell elimination process is common in the lungs and is extremely important for maintaining normal pulmonary homeostasis and tissue regeneration. Apoptotic cells have, on their surface, several molecules including phosphatidylserine (PS) and the ICAM-3, which are recognized by macrophages through a wide spectrum of receptors including receptors for PS, CD14, and CD36 [56].
Fibroblast and Immune Cell Cross Talk in Cardiac Repair
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Stelios Psarras, Georgina Xanthou
Cardiac fibroblasts affect immune cell phenotype at multiple levels during injury and repair, but they can also switch to an inflammatory phenotype themselves (Figure 5.1). Indeed, fibroblasts cultured from HF biopsies readily upregulate pro-inflammatory cytokine expression upon exposure to bacterial lipopolysaccharides (29). Following an infarct, fibroblasts transiently secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates the local recruitment of monocytes and neutrophils while it also directs a myeloid-biased differentiation program in the bone marrow (BM) (30). These systemic and local changes induce cardiac inflammation and compromise tissue rigidity, promoting ventricular wall rupture (Figure 5.1). In experimental autoimmune myocarditis, interleukin-17A (IL-17A) secretion mediates pathogenesis by stimulating cardiac fibroblasts to secrete GM-CSF, which instructs local monocyte differentiation toward the pro-inflammatory subset (Ly6Chi, expressing high levels of lymphocyte antigen 6/Ly6C) (31) (Figure 5.1). In co-culture studies, IL-17A inhibits the ability of cardiac fibroblasts to promote differentiation of monocytes to macrophages (32). Moreover, IL-17A trans-signaling stimulates the shedding of myeloid-epithelial-reproductive tyrosine kinase (MerTK) by macrophages, reducing their ability to conduct efferocytosis (32). As efferocytosis enhances anti-inflammatory signaling following engulfment of apoptotic cells, IL-17A-mediated efferocytosis inhibition confers pro-inflammatory functions to macrophages, worsening myocarditis (Figure 5.1). A stem cell antigen-1-positive (Sca1) fibroblast population has been identified in the mouse that secretes GM-CSF in an IL-17A-dependent manner and induces pro-inflammatory Ly6Chi monocyte recruitment (Figure 5.1). Importantly, IL-17A knockdown in Sca1+ fibroblasts inhibited HF features not only in autoimmune myocarditis but also in MI (33), illuminating a central role for fibro-blast-secreted IL-17A in cardiac damage.
Impact of resolvin mediators in the immunopathology of diabetes and wound healing
Published in Expert Review of Clinical Immunology, 2021
David Shofler, Vikrant Rai, Sarah Mansager, Kira Cramer, Devendra K. Agrawal
The resolution of inflammation is mediated by increasing macrophage efferocytosis. Efferocytosis is an integral part of the resolution of inflammation and is mediated by a complex and well-orchestrated network of interactions amongst specialized phagocytic receptors. Efferocytosis is defined as the engulfment of apoptotic cells by macrophages. Increased macrophage efferocytosis of the apoptotic cells and apoptotic neutrophils mediate the transformation of the inflammation phase to resolution. Efferocytosis prevents the tissues surrounding the inflamed site from being exposed to the toxic contents of lytic cells [34,35]. During this transformation, the efferocytic macrophages transform to a pro-resolving phenotype (M2 macrophages) and secrete anti-inflammatory and pro-resolving factors, including IL-10, transforming growth factor β (TGFβ), and specialized pro-resolving lipid mediators (SPM). These SPMs include resolvins, lipoxins, and maresins, which further increase the synthesis of various SPM and macrophage efferocytosis. The secretion of these pro-resolving factors dampens inflammation, potentiates resolution, and restores tissue integrity and homeostasis [19,36,37]. Macrophage efferocytosis can be increased by both resolvins and lipoxins [17,34]. Lee et al. reported that efferocytosis can be stimulated by RvD1 through p50/p50-mediated suppression of TNF-α expression using murine macrophage-like RAW264.7 cells and a murine peritonitis model [34].
Ferroptosis becomes immunogenic: implications for anticancer treatments
Published in OncoImmunology, 2021
Daolin Tang, Oliver Kepp, Guido Kroemer
Cell death and immunity are two evolutionary conserved processes that maintain homeostasis through complex molecular and cellular interactions.1 On one hand, the effective elimination of cellular debris through phagocyte-mediated efferocytosis is essential to prevent inflammatory and autoimmune diseases. On the other hand, the release or exposure of intracellular molecules from dead or dying cells can elicit adaptive immunity, which favors an immune response against intracellular pathogens as well as against tumor-associated antigens. Regarding these immunological consequences, cell death can therefore be divided into two different types: tolerogenic and immunogenic cell death (ICD).2 While the concept of ICD was originally described for chemotherapy-induced apoptotic cell death, it is now believed that ICD can occur in various types of non-apoptotic cell death caused by chemotherapy, radiotherapy, or other anticancer treatments.3 Notably, the type and activity of damage-associated molecular patterns (DAMPs) emitted during the course of cell death play a key role in determining the characteristics of ICD (Figure 1).4
Novel drug discovery strategies for atherosclerosis that target necrosis and necroptosis
Published in Expert Opinion on Drug Discovery, 2018
Isabelle Coornaert, Sam Hofmans, Lars Devisscher, Koen Augustyns, Pieter Van Der Veken, Guido R.Y. De Meyer, Wim Martinet
Clearance of dying cells by phagocytes is essential for maintaining tissue homeostasis. Phagocytic clearance of apoptotic cells (also known as efferocytosis) occurs more efficiently than that of necrotic cells [23]. However, efferocytosis in advanced atherosclerotic plaques is defective [8], which results in the accumulation of apoptotic bodies that undergo secondary necrosis. Several important functions have been attributed to efferocytosis. First, apoptotic cells are cleared at an early stage when the membrane is still intact so that secondary necrosis is prevented. Consequently, the release of inflammatory molecules such as cytokines and damage-associated molecular patterns (DAMPs) is suppressed. Second, anti-inflammatory cytokines such as tissue growth factor-β, interleukin (IL) 10, and prostaglandin E2 are secreted during efferocytosis [24,25]. It is still not entirely clear why efferocytosis is impaired in atherosclerosis. It is likely that defective efferocytosis results from multiple mechanisms including the persistent expression of ‘don’t eat me signals’ (e.g. CD47) on apoptotic cells [26], protease-mediated cleavage of efferocytosis receptors (e.g. the receptor tyrosine kinase MerTK) [27], suppression of efferocytosis-bridging molecules (e.g. lactadherin and complement factor C1q) [28,29], competition between apoptotic cells and oxidized proteins such as oxLDL and oxidized red blood cells for the recognition by phagocytes [30], and generation of autoantibodies for oxLDL that also recognize oxidized ‘eat me ligands’[31].