degranulation
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Multimodal gadolinium fluoride nanoparticles belong to potential contrast agents useful for bimodal optical fluorescence and magnetic resonance imaging. However, the metallic nature of the nanoparticles, similarly to some paramagnetic iron oxides, might induce allergic and anaphylactic reactions in patients after administration. A reduction of these adverse side effects is a priority for the safe application of the nanoparticles. Herein, we prepared paramagnetic poly(4-styrenesulfonic acid-co-maleic acid) (PSSMA)-stabilized GdF3 nanoparticles with surface modified by Atto 488-labeled poly(styrene-grad-2-dimethylaminoethyl acrylate)-block-poly(2-dimethylaminoethyl acrylate) (PSDA-A488) with reactive amino groups for introduction of an additional imaging (luminescence) modality and possible targeting of anticancer drugs. The saturation magnetization of GdF3@PSSMA particles according to SQUID magnetometry reached 157 Am2 kg-1 at 2 K and magnetic field of 7 T. GdF3@PSSMA-PSDA-A488 nanoparticles were well tolerated by human cervical adenocarcinoma (HeLa), mouse bone marrow-derived mast cells (BMMC), and rat basophilic mast cells (RBL-2H3); the particles also affected cell morphology and protein tyrosine phosphorylation in mast cells. Moreover, the nanoparticles interfered with the activation of mast cells by multivalent antigens and inhibited calcium mobilization and cell degranulation. These findings show that the new multimodal GdF3-based nanoparticles possess properties useful for various imaging methods and might minimize mast cell degranulation incurred after future nanoparticle diagnostic administration.
- MeSH
- degranulace buněk MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mastocyty * MeSH
- myši MeSH
- nanočástice * MeSH
- polymery MeSH
- růstový diferenciační faktor 3 MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
A characteristic of mast cells is the degranulation in response to various stimuli. Here we have investigated the effects of various physical stimuli in the human mast-cell line HMC-1. We have shown that HMC-1 express the transient receptor potential channels TRPV1, TRPV2 and TRPV4. In the whole-cell patchclamp configuration, increasing mechanical stress applied to the mast cell by hydrostatic pressure (–30 to –90 cm H2O applied via the patch pipette) induced a current that could be inhibited by 10 μM of ruthenium red. This current was also inhibited by 20 μM SKF96365, an inhibitor that is among TRPV channels specific for the TRPV2. A characteristic of TRPV2 is its activation by high noxious temperature; temperatures exceeding 50 °C induced a similar ruthenium-red-sensitive current. As another physical stimulus, we applied laser light of 640 nm. Here we have shown for the first time that the application of light (at 48 mW for 20 min) induced an SKF96365-sensitive current. All three physical stimuli that led to activation of SKF96365-sensitive current also induced pronounced degranulation in the mast cells, which could be blocked by ruthenium red or SKF96365. The results suggest that TRPV2 is activated by the three different types of physical stimuli. Activation of TRPV2 allows Ca2+ ions to enter the cell, which in turn will induce degranulation. We, therefore, suggest that TRPV2 plays a key role in mast-cell degranulation in response to mechanical, heat and red laser-light stimulation.
- MeSH
- buněčné linie MeSH
- degranulace buněk MeSH
- exocytóza MeSH
- kationtové kanály TRPV metabolismus MeSH
- lidé MeSH
- mastocyty fyziologie MeSH
- metoda terčíkového zámku MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Propofol has been shown to against intestinal reperfusion injury when treated either before or after ischemia, during which mast cell could be activated. The aim of this study was to evaluate the role of propofol in restoring the intestinal epithelial cells integrity disrupted by mast cell activation or the released tryptase after activation in vitro. We investigated the effect of: (1) tryptase on Caco-2 monolayers in the presence of PAR-2 inhibitor or propofol, (2) mast cell degranulation in a Caco-2/LAD-2 co-culture model in the presence of propofol, and (3) propofol on mast cell degranulation. Epithelial integrity was detected using transepithelial resistance (TER) and permeability to fluorescein isothiocyanate (FITC)-dextran (the apparent permeability coefficient, Papp). The expression of junctional proteins zonula occludens-1 (ZO-1/TJP1) and occludin were determined using western blot analysis and immunofluorescence microscopy. The intracellular levels of reactive oxidative species (ROS) and Ca2+ were measured using flow cytometry. Tryptase directly enhanced intestinal barrier permeability as demonstrated by significant reductions in TER, ZO-1, and occludin protein expression and concomitant increases in Papp. The intestinal barrier integrity was restored by PAR-2 inhibitor but not by propofol. Meanwhile, mast cell degranulation resulted in epithelial integrity disruption in the Caco-2/LAD-2 co-culture model, which was dramatically attenuated by propofol. Mast cell degranulation caused significant increases in intracellular ROS and Ca(2+) levels, which were blocked by propofol and NAC. Propofol pretreatment can inhibit mast cell activation via ROS/Ca(2+) and restore the intestinal barrier integrity induced by mast cell activation, instead of by tryptase.
- MeSH
- Caco-2 buňky MeSH
- degranulace buněk MeSH
- epitelové buňky metabolismus MeSH
- lidé MeSH
- mastocyty metabolismus MeSH
- okludin metabolismus MeSH
- permeabilita MeSH
- propofol * farmakologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- střevní sliznice metabolismus MeSH
- tryptasy metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- aktiny MeSH
- degranulace buněk MeSH
- finanční podpora výzkumu jako téma MeSH
- mastocyty fyziologie MeSH
- signální transdukce imunologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
The histamine H4 receptor regulates the inflammatory response. However, it is not known whether this receptor has a functional role in human neutrophils. We found that fMLP (1 μM), but not histamine (0.1-1 μM), induced Mac-1-dependent adhesion, polarization, and degranulation (release of lactoferrin). A pretreatment of neutrophils with histamine (0.001-1 μM) or JNJ 28610244 (0.1-10 μM), a specific H4 receptor agonist, led to inhibition of degranulation. Total inhibition of degranulation was obtained with 0.1 μM histamine and 10 μM JNJ 28610244. Furthermore, such inhibition by histamine of degranulation was reversed by JNJ 7777120 and JNJ 28307474, two selective H4 receptor antagonists. However, neither histamine nor the H4 receptor agonist JNJ 28610244 prevented fMLP-induced, Mac-1-dependent adhesion, indicating that the H4 receptor may block signals emanating from Mac-1-controlling degranulation. Likewise, engagement of the H4 receptor by the selective agonist JNJ 28610244 blocked Mac-1-dependent activation of p38 MAPK, the kinase that controls neutrophil degranulation. We also show expression of the H4 receptor at the mRNA level in ultrapure human neutrophils and myeloid leukemia PLB-985 cells. We concluded that engagement of this receptor by selective H4 receptor agonists may represent a good, therapeutic approach to accelerate resolution of inflammation.
- MeSH
- akutní promyelocytární leukemie patologie MeSH
- antigen-1 spojený s lymfocytární funkcí chemie MeSH
- buněčná adheze účinky léků fyziologie MeSH
- cytochalasin B farmakologie MeSH
- degranulace buněk * účinky léků MeSH
- fibrinogen MeSH
- histamin farmakologie MeSH
- indoly farmakologie MeSH
- konformace proteinů účinky léků MeSH
- kultivované buňky MeSH
- lidé MeSH
- makrofágový antigen 1 fyziologie MeSH
- MAP kinasový signální systém účinky léků MeSH
- messenger RNA biosyntéza genetika MeSH
- mitogenem aktivované proteinkinasy p38 fyziologie MeSH
- N-formylmethionin-leucyl-fenylalanin farmakologie MeSH
- nádorové buněčné linie MeSH
- neutrofily účinky léků fyziologie MeSH
- oximy farmakologie MeSH
- piperaziny farmakologie MeSH
- piperidiny farmakologie MeSH
- pyridiny farmakologie MeSH
- receptory histaminu fyziologie MeSH
- receptory spřažené s G-proteiny agonisté antagonisté a inhibitory fyziologie MeSH
- tvar buňky účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Chronic hypoxia induces lung vascular remodeling, which results in pulmonary hypertension. Vascular remodeling is associated with collagenolysis and activation of matrix metalloproteinases (MMPs). One of the possible sources of MMPs in hypoxic lung are mast cells. OBJECTIVE: The role of lung mast cell collagenolytic activity in hypoxic pulmonary hypertension was tested by the inhibitor of mast cell degranulation disodium cromoglycate (DSCG). METHODS: Rats were treated with DSCG in an early or later phase of isobaric hypoxia. Control groups were exposed to hypoxia only or to normoxia. Lung hemodynamics, muscularization and collagen metabolism in the walls of peripheral pulmonary vessels in the lungs were measured. RESULTS: DSCG applied at an early phase of exposure to hypoxia reduced the development of pulmonary hypertension, inhibited muscularization in peripheral pulmonary arteries and decreased the amount of collagen cleavage fragments in prealveolar vessels. CONCLUSIONS: Mast cell degranulation plays a role in the initiation of hypoxic pulmonary vascular remodeling. 2008 S. Karger AG, Basel.
- MeSH
- arteria pulmonalis metabolismus MeSH
- degranulace buněk účinky léků MeSH
- financování organizované MeSH
- hypoxie komplikace MeSH
- kolagen metabolismus MeSH
- kromoglykát dvojsodný farmakologie MeSH
- krysa rodu rattus MeSH
- mastocyty fyziologie účinky léků MeSH
- plicní hypertenze etiologie metabolismus patofyziologie prevence a kontrola MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- buňky NK fyziologie MeSH
- časové faktory MeSH
- cytotoxické T-lymfocyty fyziologie MeSH
- degranulace buněk fyziologie MeSH
- financování organizované MeSH
- imunologické testy metody MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární diagnóza imunologie metabolismus MeSH
- membránový protein 1 asociovaný s lyzozomy MeSH
- prospektivní studie MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- souhrny MeSH
