Basic Facts about Oxidative Stress, Inflammation, and the Immune System
Kedar N. Prasad in Micronutrients in Health and Disease, 2019
The immune system is a network of cells, tissues, and organs that works together in a highly coordinated manner to defend the body against foreign invading organisms or antigenic molecules or particles. The organs of the immune system are located throughout the body. They are lymphoid organs that contain lymphocytes and bone marrow that contain all blood cells, including lymphocytes. Thymus-derived lymphocytes are referred to as T-lymphocytes (T-cells). In blood, T-cell represents about 60%–70% of peripheral lymphocytes. Bone marrow-derived lymphocytes are referred to as B-lymphocytes (B-cells). They constitute about 10%–20% of peripheral lymphocytes in the blood. B-cells mature to plasma cells that secrete specific antibody in response to a particular antigen. Macrophages are derived from monocytes of bone marrow, and are a part of the mononuclear phagocyte system. They exhibit phagocytic activity and play important roles in both the induction and the effector phase of immune responses. A specialized form of cells with numerous fine dendritic cytoplasmic processes, called dendritic cells, do not exhibit phagocytic activity. They play an important role in presenting antigen to T-cells. Natural killer (NK) cells represent about 10%–15% of the peripheral blood lymphocytes and lack T-cell receptors. They can kill tumor cells.
Proinflammatory Peptides in Relation to Other Inflammatory Mediators
Sami I. Said in Proinflammatory and Antiinflammatory Peptides, 2020
The presence of tachykinin receptors on resident or circulating inflammatory cells have been proposed. Although conflicting results have been reported in the past regarding the presence of tachykinin receptors in leukocytes and particularly lymphocytes, more consistent findings indicate that cells of the monocytic lineage in the lung and outside the lung cause the release of diverse inflammatory mediators via activation of specific tachykinin receptors. Mononuclear phagocytes, either as monocytes circulating in the bloodstream or as tissue macrophages, modulate the host defense response through their ability to present antigens and the release of soluble mediators. Interleukin-1 (IL-1), TNF-α, and IL-6 were released from human blood monocytes by SP, an effect that was blocked by a SP receptor antagonist (48–50). Stimulation by naturally occurring tachykinins and by selective NK2 receptor agonists caused a respiratory burst-dependent release of superoxide anion (51) and gelantinase production (52) from rat pulmonary macrophages, thus suggesting that NK2 receptors were involved. “Nonclassical” tachykinin receptors have been proposed to be involved in cytokine release from microglia cells and macrophages (53,54).
Role of Macrophages and Endothelial Cells in Hepatotoxicity
Timothy R. Billiar, Ronald D. Curran in Hepatocyte and Kupffer Cell Interactions, 2017
Based on our current experimental data, we have proposed a model of chemically induced hepatic injury (Figure 6). According to this model, hepatocytes injured by toxicants release factors that attract Kupffer cells to specific regions of the liver. Additional mononuclear phagocytes are also recruited from blood and bone marrow precursors. Once localized in the injured area, the macrophages become “activated” by parenchymal and nonparenchymal cell-derived factors and release mediators that induce proliferation and activation of endothelial cells. Activated macrophages and endothelial cells also release mediators that contribute to damage initiated by toxicants. This eventually leads to cell death and necrosis. The data from our laboratory and those of other investigators support this model of hepatotoxicity. Additional studies on the nature of the mediators released from nonparenchymal cells and their effects on hepatocytes will be particularly relevant for understanding mechanisms of liver injury.
The Effect of CD226 on the Balance between Inflammatory Monocytes and Small Peritoneal Macrophages in Mouse Ulcerative Colitis
Published in Immunological Investigations, 2022
Juan Li, Feng Zhao, Qi Qin, Liu Yang, Yuan Jiang, Yongli Hou, Yazhen Wang, Wenjing Zhou, Liang Fang, Lihua Chen
The mononuclear phagocyte system (MPS) comprises monocytes, macrophages and dendritic cells (DCs). As one of the MPS, blood monocytes are an important defense line for intestinal immunity (Ochando et al. 2016). Human monocytes are divided into two distinct subsets: classical CD14+CD16− inflammatory monocytes (iMos) and non-classical CD14loCD16+ patrolling monocytes (pMos)(Geissmann et al. 2003; Gordon and Taylor 2005). The counterparts of these subsets are CX3CR1intCCR2+Ly6Chi monocytes (iMos) and CX3CR1hiCCR2−Ly6Clo monocytes (pMos) in mice (Geissmann et al. 2003; Gordon and Taylor 2005). Monocytes are not fully differentiated cells, and can differentiate into macrophages. There are two distinct subsets of peritoneal macrophages named large peritoneal macrophages (LPMs, CD11bhiF4/80hi) and small peritoneal macrophages (SPMs, CD11b+F4/80lo) (Ghosn et al. 2010). SPMs seem to be derived from inflammatory monocytes that are produced through hematopoiesis. LPMs appear to be independent of hematopoiesis and to be under homeostatic conditions. The abdominal and intestinal macrophages could sense and respond to invading pathogens and environmental factors. Both monocytes and macrophages are essential in maintaining intestinal health (Thiesen et al. 2014; Varol et al. 2010). Thus, a better understanding of the regulation of monocyte/macrophage differentiation is important for developing more effective therapies for UC.
Spotlight on liver macrophages for halting liver disease progression and injury
Published in Expert Opinion on Therapeutic Targets, 2022
Amit Khurana, Umashanker Navik, Prince Allawadhi, Poonam Yadav, Ralf Weiskirchen
Macrophages are mononuclear phagocytes that play a critical role in the maintenance of cellular homeostasis and are an important element of the innate immune system. Macrophages are widely distributed in lymphoid and non-lymphoid tissues throughout the body. Besides this, macrophages have several important roles in cellular debris clearance, metabolic function, tissue remodeling, and repair [12,13]. Remarkably, hepatic macrophages are the essential component of immune cells, which are linked with various hepatic disorders such as steatohepatitis, inflammation, fibrosis, as well as liver repair [14]. Additionally, in response to the local microenvironment, macrophages can be activated and polarized into different subtypes and demonstrate various cellular functions such as activation of HSCs during chronic liver injury. Further, it has been reported that the involvement of macrophages in acute and chronic hepatic damage remains controversial because of their heterogeneity and high plasticity [15–17]. The study of macrophage heterogeneity has undergone a revolution in the last five years due to the explosion in high-throughput gene expression analysis using single-cell RNA sequencing (scRNA-seq), which has greatly improved our understanding of the composition and diversity of tissue macrophages, including those in the liver. Different liver macrophage subsets have been found in mice and humans with healthy livers and liver illness using scRNA-seq. The discovery of novel pathogenic factors expressed by liver macrophages that may worsen or prevent the evolution of NAFLD was made possible using the scRNA-seq technology [18].
Effect of inflammation on cytochrome P450-mediated arachidonic acid metabolism and the consequences on cardiac hypertrophy
Published in Drug Metabolism Reviews, 2023
Mohammed A. W. ElKhatib, Fadumo Ahmed Isse, Ayman O. S. El-Kadi
The contribution of inflammatory cells to CH is well established. Macrophages (Mϕ) are mononuclear phagocytes that exert pivotal functions in tissue repair and remodeling, and regulation of adaptive and innate immunity (Murray and Wynn 2011; Takeda and Manabe 2011). In the heart, the two Mϕ phenotypes that are present are pro-inflammatory M1 and anti-inflammatory M2 (Mosser and Edwards 2008; Takeda and Manabe 2011). Regarding M1, it exacerbates cardiac inflammation through cytokine release and enhanced apoptosis, as well as its implication in cardiac remodeling (Takeda and Manabe 2011; Van den Akker et al. 2013; Fernández-Velasco et al. 2014). On the other hand, M2 attenuates inflammation and induces cardiac reparative cascades and angiogenesis (Van den Akker et al. 2013). A robust association between Mϕ and CH was created, however, reports have demonstrated that depletion of Mϕ exacerbates cardiac dysfunction following CH, proposing a pivotal undetermined contribution to both CH development and outcomes (Takeda and Manabe 2011). In summary, inflammation is a potential intervention target in CH development for discovering novel therapeutic agents that can improve the cardiac functions (Heymans et al. 2009; Hofmann and Frantz 2013).
Related Knowledge Centers
- Immunology
- Kupffer Cell
- Lymph Node
- Spleen
- Immune System
- Phagocyte
- Liver
- Monocyte
- Macrophage
- Reticular Connective Tissue