Bacteria-Host Cell Interaction Mediated by Cellular Cholesterol/Glycolipid-Enriched Microdomains

1999 ◽  
Vol 19 (5) ◽  
pp. 421-432 ◽  
Author(s):  
Jeoung-Sook Shin ◽  
Zhimin Gao ◽  
Soman N. Abraham
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Cells ◽  
Cell Interaction ◽  
The Body ◽  
Host Cells ◽  
Cell Uptake ◽  
E Coli ◽  
Close Proximity ◽  
Immunocompromised Hosts

Gram negative bacterial infection is a leading cause of fatality and is attributed, at least in part, to the bacteria's capacity to persist in the host in spite of appropriate antibiotic therapy. It has been suggested that bacteria evade antibiotics by hiding within host cells. We sought to investigate this important aspect of infections in mast cells, which are inflammatory cells found in close proximity to the host-environment interface and which have recently been reported to play a crucial role in the early innate immune response to bacteria. We examined mast cell interactions with FimH-expressing E. coli, one of the major opportunistic pathogens of humans. We determined that in serum free conditions, these bacteria were able to trigger mast cell uptake without loss of bacterial viability. CD48, a mannose containing GPI (glycosylphosphatidylinositol)-linked molecule was found to be the receptor of FimH-expressing E. coli in mouse mast cells. We found that the internalization via CD48 was blocked by filipin, a cholesterol binding drug known to disrupt cholesterol/glycolipid-enriched microdomains and the bacteria-encasing vacuoles were rich in cholesterol inside cells. Interestingly, we found that mast cells subsequently expelled majority of the intracellular bacteria in 24 hours. This expulsion process was blocked by lovastatin/cyclodextrin treatment, which is known to inhibit cellular trafficking of cholesterol/glycolipid-enriched microdomains. Thus, the bacterial entry into and expulsion from mast cells were critically dependent on cholesterol/glycolipid-enriched microdomains, which represents a novel mode of tussle between the pathogen and the mast cell occurring in opsonin deficient sites in the body or even at other sites in naive or immunocompromised hosts which have low systemic levels of E. coli specific antibody.

scholarly journals Reevaluation of reserpine-induced suppression of contact sensitivity. Evidence that reserpine interferes with T lymphocyte function independently of an effect on mast cells.

1985 ◽  
Vol 162 (6) ◽  
pp. 1935-1953 ◽  
Author(s):  
Y A Mekori ◽  
G L Weitzman ◽  
S J Galli
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Mast Cells ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Intradermal Injection ◽  
Host Cells ◽  
Lymphocyte Function

It has been suggested that reserpine blocks expression of delayed hypersensitivity (DH) by depleting tissue mast cells of serotonin (5-HT), thereby preventing a T cell-dependent release of mast cell 5-HT necessary to localize and to amplify the DH response. However, reserpine blocks expression of DH in mast cell-deficient mice. We therefore decided to reevaluate the mechanism by which reserpine abrogates expression of cellular immunity, and investigated whether the drug might interfere with T cell activity in vitro or in vivo. At concentrations as low as 4 microM, reserpine profoundly suppressed baseline or antigen-augmented levels of [3H]thymidine incorporation by immune lymph node cells obtained from mice sensitized to the contactant oxazolone [I-LNC(Ox)]. This effect was observed both with I-LNC derived from normal mice and with I-LNC derived from congenitally mast cell-deficient W/Wv mice, cell preparations that lacked detectable mast cells, histamine, and 5-HT. Furthermore, treatment of I-LNC with reserpine (20 microM) for 1 h in vitro virtually abolished the ability of these cells to transfer CS to naive mice. This was not a cytolytic effect, as the viability of the I-LNC treated with reserpine was not affected, and washing of the reserpine-treated I-LNC before transfer fully restored their ability to orchestrate a CS response. The action of the drug was not mediated by an effect on mast cells, since the experiment could be performed using mast cell-deficient W/Wv mice as both donors and recipients of I-LNC. In addition, the effect was specific for the treated cells: mice that received reserpine-treated I-LNC(Ox) intravenously together with untreated I-LNC(DNFB) did not develop CS to Ox but responded normally to DNFB; and local intradermal injection of reserpine-treated I-LNC(Ox) which failed to transfer reactivity to Ox, did not interfere with the development of CS to DNFB at the same site. Finally, cotransfer experiments indicated that the effect of reserpine on the transfer of CS was not due to activation of suppressor cells. Our findings strongly suggest that whatever effects reserpine might have on immunologically nonspecific host cells, the drug's effects on sensitized T cells are sufficient to explain its ability to block cell-mediated immune responses in vivo.

scholarly journals OOCHIP: Compartmentalized Microfluidic Perfusion System with Porous Barriers for Enhanced Cell–Cell Crosstalk in Organ-on-a-Chip

Micromachines ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 565
Author(s):  
Qasem Ramadan ◽  
Sajay Bhuvanendran Nair Gourikutty ◽  
Qingxin Zhang
Keyword(s):  
Drug Efficacy ◽  
Human Adipose Tissue ◽  
Cell Types ◽  
Cell Interaction ◽  
The Body ◽  
Close Proximity ◽  
Porous Barriers ◽  
Cell Cell

Improved in vitro models of human organs for predicting drug efficacy, interactions, and disease modelling are crucially needed to minimize the use of animal models, which inevitably display significant differences from the human disease state and metabolism. Inside the body, cells are organized either in direct contact or in close proximity to other cell types in a tightly controlled architecture that regulates tissue function. To emulate this cellular interface in vitro, an advanced cell culture system is required. In this paper, we describe a set of compartmentalized silicon-based microfluidic chips that enable co-culturing several types of cells in close proximity with enhanced cell–cell interaction. In vivo-like fluid flow into and/or from each compartment, as well as between adjacent compartments, is maintained by micro-engineered porous barriers. This porous structure provides a tool for mimicking the paracrine exchange between cells in the human body. As a demonstrating example, the microfluidic system was tested by culturing human adipose tissue that is infiltrated with immune cells to study the role if the interplay between the two cells in the context of type 2 diabetes. However, the system provides a platform technology for mimicking the structure and function of single- and multi-organ models, which could significantly narrow the gap between in vivo and in vitro conditions.

scholarly journals Enhanced mucosal permeability and nitric oxide synthase activity in jejunum of mast cell deficient mice

Gut ◽  
1997 ◽  
Vol 41 (5) ◽  
pp. 636-641 ◽  
Author(s):  
S Komatsu ◽  
M B Grisham ◽  
J M Russell ◽  
D N Granger
Keyword(s):  
Nitric Oxide ◽  
Mast Cell ◽  
Mast Cells ◽  
Inflammatory Cells ◽  
Inhibitory Influence ◽  
Mucosal Permeability ◽  
Nos Inhibitor ◽  
Plasma Nitrate ◽  
Oxide Synthase ◽  
Inducible Nos

Background—Recent reports have described a modulating influence of nitric oxide (NO) on intestinal mucosal permeability and have implicated a role for mast cells in this NO mediated process.Aims—To assess further the contribution of mast cells to the mucosal permeability changes elicited by the NO synthase (NOS) inhibitor NG-nitro-l-arginine methylester (l-NAME), using mast cell deficient (W/WV) and mast cell replete mice (+/+).Methods—Chromium-51 EDTA clearance (from blood to jejunal lumen), jejunal NOS and myeloperoxidase (MPO) activities, and plasma nitrate/nitrite levels were monitored.Results—The increased EDTA clearance elicited by intraluminal l-NAME in W/WV mice (4.4-fold) was significantly greater than the response observed in control (+/+) mice (1.8-fold). The exacerbated response in W/Wv mice was greatly attenuated by pretreatment with either dexamethasone (1.3-fold) or the selective inducible NOS inhibitor, aminoguanidine (1.4-fold), and partially attenuated by the mast cell stabiliser, lodoxamide (2.9-fold). Jejunal inducible NOS activity was significantly higher in W/WV than in +/+ mice, while jejunal MPO was lower in W/WV mice than in +/+ mice, suggesting that the higher inducible NOS in W/WV does not result from the recruitment of inflammatory cells into the gut. The higher inducible NOS activity in the jejunum of W/WV was significantly reduced by dexamethasone treatment.Conclusions—Our results suggest that mast cells normally serve to inhibit inducible NOS activity tonically in the gut and that inhibitors of NOS elicit a larger permeability response when this tonic inhibitory influence is released by mast cell depletion.

Mast cells

1997 ◽  
Vol 77 (4) ◽  
pp. 1033-1079 ◽  
Author(s):  
D. D. Metcalfe ◽  
D. Baram ◽  
Y. A. Mekori
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tissue Repair ◽  
Defense Mechanisms ◽  
Cell Activation ◽  
Allergic Inflammation ◽  
Local Environment ◽  
The Body ◽  
Mast Cell Activation ◽  
Biological Functions

Mast cells are found resident in tissues throughout the body, particularly in association with structures such as blood vessels and nerves, and in proximity to surfaces that interface the external environment. Mast cells are bone marrow-derived and particularly depend upon stem cell factor for their survival. Mast cells express a variety of phenotypic features within tissues as determined by the local environment. Withdrawal of required growth factors results in mast cell apoptosis. Mast cells appear to be highly engineered cells with multiple critical biological functions. They may be activated by a number of stimuli that are both Fc epsilon RI dependent and Fc epsilon RI independent. Activation through various receptors leads to distinct signaling pathways. After activation, mast cells may immediately extrude granule-associated mediators and generate lipid-derived substances that induce immediate allergic inflammation. Mast cell activation may also be followed by the synthesis of chemokines and cytokines. Cytokine and chemokine secretion, which occurs hours later, may contribute to chronic inflammation. Biological functions of mast cells appear to include a role in innate immunity, involvement in host defense mechanisms against parasitic infestations, immunomodulation of the immune system, and tissue repair and angiogenesis.

The distribution and genetic structure of Escherichia coli in Australian vertebrates: host and geographic effects

Microbiology ◽  
2003 ◽  
Vol 149 (12) ◽  
pp. 3575-3586 ◽  
Author(s):  
David M. Gordon ◽  
Ann Cowling
Keyword(s):  
Escherichia Coli ◽  
Body Mass ◽  
The Body ◽  
Ecological Niches ◽  
E Coli ◽  
Close Proximity ◽  
Host Diet ◽  
Group A ◽  
Human Habitation ◽  
The Tropics

Escherichia coli was isolated from more than 2300 non-domesticated vertebrate hosts living in Australia. E. coli was most prevalent in mammals, less prevalent in birds and uncommon in fish, frogs and reptiles. Mammals were unlikely to harbour E. coli if they lived in regions with a desert climate and less likely to have E. coli if they lived in the tropics than if they lived in semi-arid or temperate regions. In mammals, the likelihood of isolating E. coli from an individual depended on the diet of the host and E. coli was less prevalent in carnivores than in herbivores or omnivores. In both birds and mammals, the probability of isolating E. coli increased with the body mass of the host. Hosts living in close proximity to human habitation were more likely to harbour E. coli than hosts living away from people. The relative abundance of E. coli groups A, B1, B2 and D strains in mammals depended on climate, host diet and body mass. Group A strains were uncommon, but were isolated from both ectothermic and endothermic vertebrates. Group B1 strains could also be isolated from any vertebrate group, but were predominant in ectothermic vertebrates, birds and carnivorous mammals. Group B2 strains were unlikely to be isolated from ectotherms and were most abundant in omnivorous and herbivorous mammals. Group D strains were rare in ectotherms and uncommon in endotherms, but were equally abundant in birds and mammals. The results of this study suggest that, at the species level, the ecological niche of E. coli is mammals with hindgut modifications to enable microbial fermentation, or in the absence of a modified hindgut, E. coli can only establish a population in ‘large-bodied’ hosts. The non-random distribution of E. coli genotypes among the different host groups indicates that strains of the four E. coli groups may differ in their ecological niches and life-history characteristics.

scholarly journals Mast cell reaction to acupuncture on tongue

2019 ◽  
Vol 17 (3) ◽  
pp. 199-202
Author(s):  
N. Pirovski ◽  
Y. Staykova-Pirovska ◽  
D. Atanasova ◽  
N. Dimitrov
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Toluidine Blue ◽  
Sagittal Plane ◽  
Acupuncture Point ◽  
Visualization Method ◽  
Cell Reaction ◽  
Acupuncture Needle ◽  
Needle Tract ◽  
Close Proximity

PURPOSE: The aim is to find out the mast cells (MCs) reaction in tongue after experimental acupuncture. METHODS: For experiments were carried 10 adults rats (28 months age). The needles used for the acupuncture is 0.22x13mm, and were placed for 10 minutes into standard acupuncture point Ex-HN-10 (Juquan) corresponding to that of humans. This point is located on the upper surface in the sagittal plane of the tongue and is close to the center of the tongue body. As normal consequence of every acupuncture is the forming of a needle tract and also here in the tissues of the rats tongue we could demonstrate this. This was done with a visualization method for the needle tract that we developed for tongue. The proximity of the needle tract was examined for MCs. Two stains were used for proper visualization: Toluidine blue and Bismarck brown staining. RESULTS: In close proximity of the needle tract we observed degranulation of MCs that was massive and few destroyed MCs in the needle tract itself. At a considerable distance from the MCs some discharged granules from them was found. CONCLUSIONS: There is a MCs reaction on the acupuncture of tongue that includes a degranulation of the MCs that was massive in proximity of the acupuncture needle tract. Some of the effects ot acupuncture could be due to the demonstrated MCs degranulation.

scholarly journals Borrelia burgdorferiSpirochetes Induce Mast Cell Activation and Cytokine Release

1999 ◽  
Vol 67 (3) ◽  
pp. 1107-1115 ◽  
Author(s):  
Jeffrey Talkington ◽  
Steven P. Nickell
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Cell Types ◽  
Host Cells ◽  
Mast Cell Activation ◽  
Cytokine Release ◽  
Necrosis Factor Alpha ◽  
Tnf Α

ABSTRACT The Lyme disease spirochete, Borrelia burgdorferi, is introduced into human hosts via tick bites. Among the cell types present in the skin which may initially contact spirochetes are mast cells. Since spirochetes are known to activate a variety of cell types in vitro, we tested whether B. burgdorferi spirochetes could activate mast cells. We report here that freshly isolated rat peritoneal mast cells or mouse MC/9 mast cells cultured in vitro with live or freeze-thawed B. burgdorferi spirochetes undergo low but detectable degranulation, as measured by [5-3H] hydroxytryptamine release, and they synthesize and secrete the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In contrast to findings in previous studies, where B. burgdorferi-associated activity was shown to be dependent upon protein lipidation, mast cell TNF-α release was not induced by either lipidated or unlipidated recombinant OspA. This activity was additionally shown to be protease sensitive and surface expressed. Finally, comparisons of TNF-α-inducing activity in known low-, intermediate-, and high-passage B. burgdorferi B31 isolates demonstrated passage-dependent loss of activity, indicating that the activity is probably plasmid encoded. These findings document the presence in low-passage B. burgdorferi spirochetes of a novel lipidation-independent activity capable of inducing cytokine release from host cells.

Abstract 15720: Transmembrane Stem Cell Factor Delivered in Nanocarriers Promotes Angiogenesis in Ischemia Without Mast Cell Activation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Eri Takematsu ◽  
Sanjana Srinath ◽  
Michael Sherman ◽  
Andrew K Dunn ◽  
Aaron Baker
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
The Body ◽  
Mast Cell Activation ◽  
Protein Therapy ◽  
Current Standard ◽  
Therapeutic Benefits

Introduction: The current standard cares for peripheral artery disease (PAD) include surgical revascularizations with bypass grafting or percutaneous interventions. However, these interventions cannot be performed in a significant portion of patients, and many do not respond to these surgical procedures. Protein therapy to stimulate the body to create new vasculature is another alternative, which is minimally invasive to patients. Stem cell factor (SCF) is a candidate protein for treating PAD, but clinical use of SCF has been limited due to toxicity related to mast cell activation. SCF also exists in a transmembrane form (tmSCF), possessing differential activities from soluble SCF and has not been explored as a therapeutic agent. Results: To develop tmSCF as a therapeutic we created tmSCF embedded in liposome or lipid nanodisc (Fig. A) . Hindlimb ischemia model on WT and ob/ob mice showed that tmSCF proteliposome (tmSCFPL) and nanodisc (tmSCFND) improved blood flow recovery significantly more than control (Fig. B, C) . Mouse model of anaphylaxis revealed that tmSCF-based therapies did not activate mast cells (Fig. D, E) . Colocalization assay of c-Kit and clathrin/caveolin revealed that mast cells preferentially use clathrin-mediated pathways to internalize SCF and caveolin-mediated pathways for tmSCF-based therapies (Fig. F, G) . Surface c-Kit internalization study on mast cells showed faster uptake of SCF in comparison to tmSCF-based therapies (Fig. H) . Previous study indicates that clathrin-mediated internalization causes increased activation of mast cells. Our studies together with the previous finding suggest that mast cell activation does not occur for tmSCF-based therapies because of the slower uptake, greater utilization of the caveolin internalization pathway and weaker activation of mast cells. Conclusions: TmSCF-based therapies can provide therapeutic benefits without off-target effects on mast cells by tuning activation with nanocarriers.

scholarly journals A Comparative Analysis of Mast Cell Quantification in Five Common Dermatoses: Lichen Simplex Chronicus, Psoriasis, Lichen Planus, Lupus, and Insect Bite/Allergic Contact Dermatitis/Nummular Dermatitis

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Nikhil Patel ◽  
Amir Mohammadi ◽  
Ronald Rhatigan
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Large Body ◽  
Dendritic Morphology ◽  
Hair Follicles ◽  
The Body ◽  
Tissue Sections ◽  
Lichen Simplex Chronicus ◽  
Allergic Contact

There is a large body of literature demonstrating an important role of mast cells in adaptive and innate immunity. The distribution of mast cells in the skin varies in different parts of the body. It is well known that mast cells are important for effector functions of classic IgE-associated allergic disorders as well as in host defense against infective agents and influence the manifestation of autoimmune diseases. We aimed to quantify mast cells in five common dermatoses and compare them statistically with respect to the immunostains. We retrieved paraffin-embedded tissue sections from the archives of the Pathology Department at the UF, Jacksonville, for five cases with each of the above diagnosis from the last three years. We performed CD-117 and tolidine blue stains on each one of them. The presence or absence of mast cells was evaluated and quantified. We observed that, in the skin, mast cells are mainly located close to the vessels, smooth muscle cells, hair follicles, and nerve ending. Our study showed that the mast cell distribution pattern is different across the two methods of staining for the five aforesaid dermatoses. The other important observation was the dendritic morphology of the mast cells.

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