Current in vivo Models for Brain Disorders
Carla Vitorino, Andreia Jorge, Alberto Pais in Nanoparticles for Brain Drug Delivery, 2021
Nanotechnology has also offered the first rays of hope in the treatment for neuroAIDS, which until the date has no effective vaccines or specific drug therapy. Dou et al. have developed a macrophage-based NP platform for antiretroviral drug delivery [36]. They designed a novel bone marrow-derived macrophage (BMM) pharmacologic NP delivery system. Hypothesising that the system will improve drug distribution to areas of active viral replication, and extend dosing intervals and this way achieving therapeutic efficacy. Their model was based on loading indinavir (antiretroviral drug) nanosuspension into BMMs (NP-IDV-BMMs) and administered intravenously into naive mice or NOD/SCID mice humanised with human peripheral blood lymphocytes reconstitution infected with human immunodeficiency virus 1 (HIV-1). Cell tissue distribution was tracked by single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) of radio- and superparamagnetic iron oxide (SPIO; Feridex)-labelled BMMs, and confirmed by histology. Antiretroviral therapeutic responses and immune response were studied in humanised infected mice.
Dopamine in the Immune and Hematopoietic Systems
Nira Ben-Jonathan in Dopamine, 2020
Activation of immunologic responses appears to have an important role in PD pathology [50]. For example, microglia show greater phagocytic activity in the substantia nigra of the brain of PD patients than in controls. Microglia are bone marrow-derived macrophage-like cells that are resident within the CNS. They constitute 20% of the total glial population and represent the first line of immune defense in the brain. Microglia activation is characterized by proliferation, migration, expression of the immune-related antigens and transformation into phagocytes. In addition to the phagocytosis of dopaminergic neurons by microglia, intraneuronal accumulation of alpha-synuclein (α-Syn), as the main pathological hallmark of PD, potentially mediates initiation of the autoimmune and inflammatory events through auto-reactive T cells.
Cryptococcosis
Rebecca A. Cox in Immunology of the Fungal Diseases, 2020
In contrast to studies of normal phagocytic mononuclear cells, in vivo stimulated or activated macrophages possess varying degrees of anticryptococcal activity.120,124-126,138,140,141,147,148 For example, rat glycogen-stimulated peritoneal macrophages, in the presence of 20% fresh isologous serum, limited the growth of some of the ingested C. neoformans cells; however, most of the phagocytized yeast cells remained viable.125 Other investigators have shown pyran copolymer-elicited peritoneal exudate cells (PEC) from mice had enhanced phagocytic and cryptococcocidal abilities when compared to thioglycollate-induced PEC.147 Activation of macrophages via cell-mediated immune mechanisms enhances anticryptococcal activity.126,148 Mouse bone-marrow-derived macrophage cell lines, which have characteristics of activated macrophages, have also been reported to inhibit the growth of cryptococci in vitro.138 Maximum growth inhibition was attained in those studies when 8 to 12% fresh mouse serum was present in the medium.138 The requirement of a serum factor for activated macrophage phagocytosis and fungistasis of C. neoformans has been confirmed and investigated by Granger et al.141
Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages
Published in OncoImmunology, 2018
Dörthe Masemann, Katharina Köther, Meike Kuhlencord, Georg Varga, Johannes Roth, Brian Dennis Lichty, Ulf Rüdiger Rapp, Viktor Wixler, Stephan Ludwig
HeLa cells were incubated for 30 min with 10 µg/ml Mitomycin in suspension to block cell proliferation and seeded with 1× 104 cells in 100 µl DMEM per well. The next day, bone marrow-derived macrophages that have been pre-stimulated o/n with 1 µg/ml LPS were resuspended in either WT or Raf-BxB BALF and added to HeLa cells with 100 µl per well. The final effector-target-cell ration was 20:1 and the final dilution of BALF, 1:20. After 48 h of co-culture, cells were detached and stained for bone-marrow derived macrophage marker. The absolute number of cells per sample was calculated using flow cytometry cell counting beads (Thermo Fisher Scientific, Cat. No.: C36950) as described by the manufacturer and the number of remaining non-lysed HeLa cells was calculated after gating out the CD11b+ and F4/80+ macrophages.
YjbH mediates the oxidative stress response and infection by regulating SpxA1 and the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) in Listeria monocytogenes
Published in Gut Microbes, 2021
Changyong Cheng, Xiao Han, Jiali Xu, Jing Sun, Kang Li, Yue Han, Mianmian Chen, Houhui Song
RNA extraction and purification from intracellular bacteria grown in bone marrow-derived macrophage cells (BMDMs) were carried out as previously described.69 BMDMs were isolated from 6–8 week-old female C57BL/6 mice and cultured in DMEM supplemented with 20% FBS, 1% L-glutamine, 1% sodium pyruvate, 14 mM 2-mercaptoethanol, and 10% 3T3 cell supernatant (from MCSF-producing 3T3 cells).70,71 Briefly, L. monocytogenes were used to infect BMDMs seeded in a 145 mm dish, resulting in a MOI of ~100. After 30 min infection, cells were washed twice with PBS to remove unattached bacteria, and fresh medium was added. At 1 h post-infection, gentamicin (50 μg/ml) was added to kill extracellular bacteria. At 6 h post-infection, intracellular bacteria were collected using 0.45 μM filter membranes and flash-freezed in liquid nitrogen. Total bacterial RNA was extracted and purified using the Trizol method and then subjected to the following transcriptional analysis.
Activation of aryl hydrocarbon receptor (AhR) in mesenchymal stem cells modulates macrophage polarization in asthma
Published in Journal of Immunotoxicology, 2020
Zhuang Cui, Yuan Feng, Danqing Li, Taoping Li, Peisong Gao, Ting Xu
Male C57BL/6J mice (6–8 weeks of age for isolation of MSC, 8–10 weeks of age for bone marrow-derived macrophage [BMDM] differentiation) were purchased from the Experimental Animal Centre of Southern Medical University (Guangzhou, China). All mice were housed in a pathogen-free university animal facility maintained at 25 °C with a 50% relative humidity and a 12-h light:dark cycle. All mice had ad libitum access to standard rodent chow and filtered tap water. All animal experiments performed here were approved by the Southern Medical University Animal Ethics Committee and were performed in accordance with the Committee’s guidelines.
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