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Dynein in Endosome and Phagosome Maturation
Published in Keiko Hirose, Handbook of Dynein, 2019
Ashim Rai, Divya Pathak, Roop Mallik
The end of this stage is marked by a transition in which the Rab5 GTPase is replaced by Rab7 and late stage markers such as LAMP-1 appear on the phagosome [75]. This stage is characterized by the rapid dynein-dependent transport of the “late phagosomes” towards the perinuclear degradative compartment of the lysosomes. The final stage involves fusion of late phagosomes with the lysosome to form a phagolysosome. Acid hydrolases and other enzymes degrade the internalized particle and may release the products to be utilized by the cell. Autophagosomes also switch from bidirectional to retrograde motion as they mature in primary neurons [49]. Therefore, understanding the mechanism of this switch that promotes dynein driven motion is important for all cell types.
Cytotoxicology Studies of 2-D Nanomaterials
Published in Suresh C. Pillai, Yvonne Lang, Toxicity of Nanomaterials, 2019
Priyanka Ganguly, Ailish Breen, Suresh C. Pillai
NMs of size <200 nm are taken up via phagocytosis. It is utilised by several mammalian cells such as the mononuclear phagocytes, macrophages, and neutrophils to eliminate infectious particles or cellular debris. These specialised cells have advanced their operational ability and contribute in the intake of nutrients, development and remodelling of tissues, and immune response and inflammation. The ligands on the particles interact with the receptors of the cell to initiate the internalisation process (Sbarra and Karnovsky, 1959; Stossel, 1974). The ingestion process of the NMs by phagocytosis process is speeded up by the presence of specialised molecules such as antibodies, labelled on the surface of the ingested particle; this technique of labelling is termed opsonization. Additionally, this results in polymerization of actin and the ingestion of the particles via an actin-based mechanism. The lysosomes (contains digesting enzymes) combine with the phagocytic cells to form phagolysosomes. The nature of the surface interaction between the particle and the phagosome membrane determines the time for this fusion (Aderem and Underhill, 1999; Allen and Aderem, 1996). Various proteases and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are used for the complete disintegration of the ingested particles inside the compartment. The remaining cell debris after the disintegration process is excreted via exocytosis (Buzea et al., 2007). The existence of different types of receptors and the alteration of the individual fate of the ingested particles make this process of phagocytosis extremely complex in nature. The key defining task of these cells is to distinguish between potential pathogens and itself. Nevertheless, this task is completed by numerous phagocytic receptors which have the ability to differentiate between them (Champion and Mitragotri, 2006; Indik et al., 1995).
Biocompatibility of Elastomers
Published in Severian Dumitriu, Valentin Popa, Polymeric Biomaterials, 2020
Dominique Chauvel-Lebret, Pascal Auroy, Martine Bonnaure-Mallet
Macrophages appear to play a predominant role in the degradation of elastomers. They are involved in the pinocytosis and phagocytosis of cell and tissue debris as well as polymer contaminants on the surfaces of biomaterials. Phagolysosomes digest the particles they have ingested and the degradation products are then released into the extracellular environment together with lysosomal enzymes, peroxides, and hydrogen ions (Collier et al. 1998, Marchant et al. 1984b, Szycher and Reed 1992, Tang and Eaton 1995). Lysosomal enzymes like enzymes—cholesterol esterase (CE) and phospholipase A2 (PLA) have often been implicated in the degradation process despite the difficulties in analyzing this phenomenon in vivo (Labow et al. 1997, Marchant et al. 1984a). The release of lysosomal enzymes, peroxides, and hydrogen ions, which are very concentrated at the cell/polymer surface interface, leads to significant degradation at this site. The degradation is faster for porous elastomers than dense elastomers. Stress and tension combined with the chemical properties of the elastomer are also involved in the degradation process (Collier et al. 1998). Degradation leads to surface cracking and a loss of molecular weight, which in turn results in a loss of tensile strength (Pinchuk 1994).
Docosahexaenoic acid impacts macrophage phenotype subsets and phagolysosomal membrane permeability with particle exposure
Published in Journal of Toxicology and Environmental Health, Part A, 2021
Paige Fletcher, Raymond F. Hamilton, Joseph F. Rhoderick, James J. Pestka, Andrij Holian
Once the particles are phagocytosed by AM they are enclosed in a phagolysosome where foreign material is intended to be degraded in order to maintain homeostasis. However, non-degradable particles can induce LMP which leads to NLRP3 inflammasome formation and activation of the inflammatory pathway cascade. Since the macrophage phenotypes exhibited differences in particle uptake, alterations in the stability of the phagolysosomal membrane was assessed after 4-hr particle incubation. LMP was determined by β-N-acetylglucosaminidase (NAG) activity; a lysosomal-specific enzyme, in the cytosolic fraction of AM polarized into the various phenotypes. Results showed that MWCNT exposure caused a significant particle-induced increase of LMP only in the M2c AM which is consistent with the increased release of IL-1β in this same phenotype. However, upon DHA treatment both M2c (Figure 4(e)) and M0 (Figure 4(a)) AM displayed trending decreases in NAG release for MWCNT exposures and a significant decrease in NAG release with DHA treatment for SiO2 exposures compared to media-only controls. These results indicate less LMP which correlates with enhanced phagolysosomal membrane stability. In contrast, M1 (Figure 4(b)) and M2a (Figure 4(c)) AM showed elevated NAG release upon DHA treatment compared to media-only controls for both particle exposures suggesting an increase in LMP which correlates to a reduction in phagolysosomal membrane stability. The M2b AM remained unchanged by DHA treatment compared to the media-only control for either particle (Figure 4(d)). The results demonstrated that DHA stabilized the phagolysosomal membrane of the M0 and M2c AM after particle exposure. The benefits of DHA treatment for particle-induced LMP ranked M2c>M2b>M2a>M1 for the AM phenotypes. Taken together for the in vitro studies, DHA affected the manner in which macrophages take up particles and alter the phagolysosomal membrane; both which differ among the macrophage phenotypes. In particular, upon DHA treatment the M2c phenotype stabilized the phagolysosomal membrane and decreased cytotoxicity regardless of enhanced particle uptake. As opposed to the M2a phenotype where DHA also increased particle uptake, but resulted in elevated LMP and enhanced cytotoxicity. This supports the hypothesis that particle-induced inflammatory responses were not uniform across different macrophage phenotypes; however, DHA did not always downregulate the inflammatory responses.