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Tumor Necrosis Factor
Published in Jason Kelley, Cytokines of the Lung, 2022
Alveolar macrophages are constitutively present in the normal lung under physiological conditions. Alveolar macrophages reside within alveolar spaces and, with their great phagocytic capacity (Ulich et al., 1991a), are the first line of defense against microorganisms and foreign matter. Interstitial macrophages are present within the alveolar wall. Monocytes leave the circulation to appear in the alveolar space within the first 24 h of an acute inflammatory reaction (Ulich et al., 1991a). In addition to serving as the most likely major source for TNF production in the lung, monocytes and alveolar macrophages are target cells for TNF. It activates macrophages to enhance their cytolytic activity, to express lipid modulators of inflammation, such as PGE2, and to amplify the inflammatory response by the elaboration of further cytokines, such as IL-1, colony-stimulating factors, and even TNF itself (Grunfeld and Palladino, 1990; Phillip and Epstein, 1986; Oster et al., 1987). Human monocyte-derived macrophages are stimulated by TNF to inhibit the growth of atypical intracellular mycobacteria (Denis, 1991), a finding of potential clinical significance to patients with acquired immunodeficiency syndrome (AIDS) who have pulmonary and systemic atypical mycobacterial infection.
Challenges in Delivering Gene Therapy
Published in Yashwant Pathak, Gene Delivery, 2022
DNA delivery starts from a multistep process that begins with DNA condensation, introduction of DNA to systemic circulation, targeted delivery followed by the unpacking of DNA, and translation into the eukaryotic cell [25]. The key is success and to overcome the challenge of DNA delivery, the mechanism of delivery must be thoroughly considered in design such that there is a maximization of therapeutically active DNA and a minimization of side effects. Once condensation of DNA is completed, a critical challenge of navigating through the extracellular barriers becomes prominent. The infamous immune response is the most likely to occur as an extracellular barrier. In the lungs, alveolar macrophages come in response to a triggered immune response. These macrophages are phagocytic cells that consume cells that pose a threat to the system [32]. Generally, immune responses are triggered by viral vectors, but there have been instances where non-viral vectors have activated an immune response. One example is when cationic lipoplexes are intravenously injected into the patient, they can induce an inflammatory response which involves the release of TNFα and IFNγ into the serum [33].
The Toxic Environment and Its Medical Implications with Special Emphasis on Smoke Inhalation
Published in Jacob Loke, Pathophysiology and Treatment of Inhalation Injuries, 2020
Jacob Loke, Richard A. Matthay, G. J. Walker. Smith
Alteration in alveolar macrophage chemotactic function also has been demonstrated (Demarest et al., 1979). In laboratory animals, alveolar macrophage chemotactic function may actually be increased after minimal inhalation of pyrolysis products of Douglas fir wood. However, with higher levels of inhalational exposure (reflected by a carboxyhemoglobin level of about 20 percent), there is impairment in alveolar macrophage chemotactic function (Loke et al., 1981a). In addition, after exposure to wood smoke, alveolar macrophage show surface characteristics change and these cells are smaller by scanning electron microscopy. Moreover, these cells show altered cytoplasmic morphology, display decreased surface adherence, and exhibit diminished phagocytic and bactericidal function (Loke et al., 1984; Fick et al., 1984). These alterations in pulmonary alveolar macrophage structure and function decrease lung defense barriers, and may explain in part the increased susceptibility of patients with smoke inhalation to pulmonary infection.
Multiple pathways of alveolar macrophage death contribute to pulmonary inflammation induced by silica nanoparticles
Published in Nanotoxicology, 2021
Eun-Jung Park, Min-Sung Kang, Seung-Woo Jin, Tae Geol Lee, Gwang-Hee Lee, Dong-Wan Kim, Eun-Woo Lee, Junhee Park, Inhee Choi, Youngmi Kim Pak
Inhalation is a main way that airborne pollutants and pathogenic microbes enter the human body, and it has been well known that nano-sized particles can more easily reach the alveoli compared to micro-sized particles. Alveolar macrophages also cover the first line of defense against unwanted substances enter the respiratory system, initiating an innate immune response in the lung (Hu and Christman 2019). Therefore, their dysfunction can be linked to various pulmonary diseases together with lung tissue damage. In our previous study, 20 nm-sized amorphous silica nanoparticles (20-SiNPs), but not 50 nm-sized amorphous silica nanoparticles (50-SiNPs), induced an inflammatory response in the lungs of rats exposed repeatedly via the trachea for 14 days (three times per week, total six times, Han et al. 2020). In addition, when exposed to human carcinoma cell lines which derived different origins lung (epithelial-like) (A549), colon (large intestine) epithelial (SW480) for 24 h (5 − 500 μg/mL), and hepatocellular (epithelial-like) (HepG2), smaller SiNPs (20 and 30 nm in diameter) more notably decreased cell viability compared to larger SiNPs (40 and 50 nm in diameter) (Kim et al. 2019), and only the 20-SiNPs induced significant apoptotic and necrotic cell death via ROS-mediated ER stress in cells derived from human umbilical cord veins (Lee et al. 2019). Therefore, in the current study, we aimed to identify the underlining causes of different pulmonary responses induced by both SiNPs using mice and mouse alveolar macrophage cells.
Aggravation of atherosclerosis by pulmonary exposure to indium oxide nanoparticles
Published in Nanotoxicology, 2020
Dong-Keun Lee, Hyung Seok Jang, Hyunji Chung, Soyeon Jeon, Jiyoung Jeong, Jae-Hoon Choi, Wan-Seob Cho
Previously, it was reported that CD11b expression is increased in alveolar macrophages during acute and chronic lung inflammation (Duan et al. 2012, 2016; Johnston et al. 2012). Therefore, we analyzed the phenotypic changes in alveolar macrophages using flow cytometry. Representative gating strategies are shown in Figure 3(A). Briefly, single cells from the lung were gated according to their levels of forward-scattered light (FSC) and side-scattered light (SSC). Then, the leukocytes expressing CD45, a common marker of leukocytes, were analyzed; these included alveolar macrophages (CD11chiCD64+), CD11b+ alveolar macrophages (CD11b+CD11chiCD64+), interstitial macrophages (CD11cloMerTK+CD64+), and dendritic cells (CD64lo-negCD11chiMHCIIhi). The total leukocyte count in the right caudal lobe of the lung was not different between the vehicle and NP-treated groups. Although the number of alveolar macrophages was not significantly different in the In2O3 NP-treated groups compared with the control group, the CD11b expression on the alveolar and interstitial macrophages was markedly increased after treatment with In2O3 NPs (Figure 3(B–D)). The number of dendritic cells was decreased in the lung tissue treated with In2O3 NPs (Figure 3(E)). These results indicated that treatment with In2O3 NPs increased the number of inflammatory alveolar macrophages expressing CD11b.
Alfa-1-antitrypsin deficiency: a predisposing factor leading to invasive infections?
Published in Infectious Diseases, 2020
Sanne De Smet, Jan Dierick, Sophia Steyaert, Marie Schurgers, Christophe Van Steenkiste, Sarah Loof
The first mechanism is the dysfunction of the alveolar macrophages. Alveolar macrophages are the primary phagocytes of the innate immune system, clearing the air spaces of infectious, toxic, or allergic particles that have evaded the mechanical defences of the respiratory tract. Besides that, they also function as regulators of innate alveolar defences against respiratory infection. They initiate inflammatory responses and recruit activated neutrophils into the alveolar spaces and they are important for the clearance of apoptotic neutrophils. In a mice model of experimental pneumococcal pneumonia, depletion of alveolar macrophages led to failure to clear apoptotic neutrophils. Consequently, the persistent production of pro-inflammatory cytokines, influx of activated neutrophils, and alveolar capillary injury, led to a higher mortality rate in comparison with ‘normal mice’ [11,13].