Chitosan‐induced phospholipase A<sub>2</sub> activation and arachidonic acid mobilization in P388D<sub>1</sub> macrophages

Bianco, Ismael D.; Balsinde, Jesús; Beltramo, Dante M.; Castagna, Leonardo F.; Landa, Carlos; Dennis, Edward A.

doi:10.1016/s0014-5793(00)01089-9

Cited by 34 publications

(20 citation statements)

References 21 publications

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“…NK cells are known to be involved in clearance of cells infected with intracellular pathogens, but the relevance of NK cells in our model is unclear. Limited but detectable macrophage infiltration was observed in the footpads of animals not sensitized with C. albicans and challenged with chitosan, indicating that macrophages may respond to stimulation by chitosan directly and independently of T-cells, probably through innate immune receptors, as has been demonstrated in the literature (Bianco et al, 2000;Peluso et al, 1994) Given the flexibility, consistency, and sensitivity of the ex vivo ELISPOT-based DTH assay, this method provides a great complement to the more traditional in vivo footpad swelling DTH assay in adult rats, and offers clear advantages for immunotoxicity testing in neonatal/juvenile animals. Further validation of this model using a range of immunotoxic compounds with known effects in humans is needed.…”

Section: Discussionsupporting

confidence: 54%

Evaluation of a novel delayed-type hypersensitivity assay toCandida albicansin adult and neonatal rats

Thorn¹,

Hudson²,

Kreeger

et al. 2014

Journal of Immunotoxicology

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Delayed-type hypersensitivity (DTH) is a T-cell-mediated immune response that may be used for immunotoxicity testing in non-clinical species. However, in some cases DTH assays using T-dependent antigens may be confounded by the production of antibodies to the antigen. The authors have previously modified a DTH assay, initially validated in the mouse, for use in juvenile rats to assess the effect of immunosuppressive drugs on the developing rat immune system. The assay measures footpad swelling induced by subcutaneous footpad injection of Candida albicans (C. albicans) derived-chitosan in rats previously sensitized with C. albicans. Antibodies to chitosan are not produced in this model. However, considerable inter-animal variability inherent in the footpad swelling assay can make it difficult to precisely quantify the magnitude of the immune response and inhibition by immunosuppressants, particularly if complete suppression is not observed. This report describes the development of an ex vivo assay to assess DTH in rats using interferon (IFN)-g production by splenocytes, obtained from rats sensitized with C. albicans, as the quantifiable measure of the DTH response. Adult and neonatal rats administered dexamethasone (DEX), a known immunosuppressant, exhibited immunosuppression as evidenced by a reduction in ex vivo IFNg production from splenocytes challenged with C. albicans-derived chitosan. Current data indicate that the ex vivo based DTH assay is more sensitive than the conventional footpad swelling assay due to a lower background response and the ability to detect a response as early as post-natal day (PND) 12. The ex vivo based rat DTH assay offers a highly sensitive and quantitative alternative to the footpad swelling assay for the assessment of the immunotoxic potential of drugs. The increased sensitivity of the ex vivo DTH assay may be useful for identifying smaller changes in response to immunotoxic drugs, as well as detecting responses earlier in animal development.

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Section: Discussionsupporting

confidence: 54%

Evaluation of a novel delayed-type hypersensitivity assay toCandida albicansin adult and neonatal rats

Thorn¹,

Hudson²,

Kreeger

et al. 2014

Journal of Immunotoxicology

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“…LPS present in TE was determined by using the Endosafe Limulus Amebocyte Lysate test (Charles River Laboratories Wilmington, DE), and was similar to that of complete RPMI 1640 medium supplemented with 10% fetal calf serum (FCS; Gibco, Gran Island, NY), 50 µM 2-mercaptoethanol (Sigma-Aldrich, St Louis, MO) and 50 µg/ml Gentamicin (Gibco). CII was prepared as described [15]. CpG-ODN 1826 was purchased from OPERON (Huntsville, AL).…”

Section: Methodsmentioning

confidence: 99%

Helminth Antigens Enable CpG-Activated Dendritic Cells to Inhibit the Symptoms of Collagen-induced Arthritis through Foxp3+ Regulatory T Cells

et al. 2012

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Dendritic cells (DC) have the potential to control the outcome of autoimmunity by modulating the immune response. In this study, we tested the ability of Fasciola hepatica total extract (TE) to induce tolerogenic properties in CpG-ODN (CpG) maturated DC, to then evaluate the therapeutic potential of these cells to diminish the inflammatory response in collagen induced arthritis (CIA). DBA/1J mice were injected with TE plus CpG treated DC (T/C-DC) pulsed with bovine collagen II (CII) between two immunizations with CII and clinical scores CIA were determined. The levels of CII-specific IgG2 and IgG1 in sera, the histological analyses in the joints, the cytokine profile in the draining lymph node (DLN) cells and in the joints, and the number, and functionality of CD4+CD25+Foxp3+ T cells (Treg) were evaluated. Vaccination of mice with CII pulsed T/C-DC diminished the severity and incidence of CIA symptoms and the production of the inflammatory cytokine, while induced the production of anti-inflammatory cytokines. The therapeutic effect was mediated by Treg cells, since the adoptive transfer of CD4+CD25+ T cells, inhibited the inflammatory symptoms in CIA. The in vitro blockage of TGF-β in cultures of DLN cells plus CII pulsed T/C-DC inhibited the expansion of Treg cells. Vaccination with CII pulsed T/C-DC seems to be a very efficient approach to diminish exacerbated immune response in CIA, by inducing the development of Treg cells, and it is therefore an interesting candidate for a cell-based therapy for rheumatoid arthritis (RA).

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“…The relatively higher values observed for CBC when compared to commercial dressings may be related to the effect of the material bioconversion products, but also to a certain pro-inflammatory activity of CBC [90]. Bianco et al [91] reported that chitosan could mediate macrophage activation through the release of arachidonic acid (AA) and even found higher levels of cytokines released from LPSstimulated cells in the presence of chitosan. Moreover, it was found that chitosan amino groups are recognized by the immune system and that macrophages are activated to various extents by chitin derivatives.…”

Section: Cytocompatibility and Anti-inflammatory Activitymentioning

confidence: 99%

Wound dressings loaded with an anti-inflammatory jucá (Libidibia ferrea) extract using supercritical carbon dioxide technology

Dias

Rey‐Rico

Oliveira

et al. 2013

The Journal of Supercritical Fluids

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a b s t r a c t N-Carboxybutyl chitosan (CBC), collagen/cellulose (Promogran ® ) and hyaluronic acid-based (Hyalofill ® ) polymeric matrices/dressings were loaded with an extract obtained from jucá (Libidibia ferrea) and in order to develop wound dressings endowed with anti-inflammatory activity. Jucá fruits were subjected to supercritical fluid extraction (SFE) using CO 2 at 25 MPa and 50• C and the resulting extract was later incorporated into the above referred wound dressings by a supercritical fluid impregnation/deposition method (SSI). GC analysis revealed that the obtained SFE extract is particularly rich in unsaturated (52%) and saturated (26%) fatty acids as well as in terpenoids (13%) such as lupenone and gamma-sitosterol. Extract loading yields depended on the affinity of the hydrophobic extract for the specifically employed wound dressing material and was almost 2-fold greater for CBC than for the other two commercial wound dressings. The prepared extract-loaded dressings were cytocompatible with RAW 264.7 macrophages (viability > 85% at 24 h) and down-regulated the expression of TNF-␣ and IL-1␣ proinflammatory cytokines as well as the production of nitric oxide, which confirms the anti-inflammatory capacity of the employed jucá extract. Nevertheless, such effect was somehow counteracted by a proinflammatory activity that was exhibited by CBC. Prepared dressings presented a wide range of water vapor ((2.9-14.7) × 10 14 kg/(s m Pa)) and oxygen permeability (150 up to 830 barrer) which make them potentially suitable for the management of various wound types at different healing stages.

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Chitosan‐induced phospholipase A₂ activation and arachidonic acid mobilization in P388D₁ macrophages

Cited by 34 publications

References 21 publications

Evaluation of a novel delayed-type hypersensitivity assay toCandida albicansin adult and neonatal rats

Evaluation of a novel delayed-type hypersensitivity assay toCandida albicansin adult and neonatal rats

Helminth Antigens Enable CpG-Activated Dendritic Cells to Inhibit the Symptoms of Collagen-induced Arthritis through Foxp3+ Regulatory T Cells

Wound dressings loaded with an anti-inflammatory jucá (Libidibia ferrea) extract using supercritical carbon dioxide technology

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Chitosan‐induced phospholipase A2 activation and arachidonic acid mobilization in P388D1 macrophages

Cited by 34 publications

References 21 publications

Evaluation of a novel delayed-type hypersensitivity assay toCandida albicansin adult and neonatal rats

Evaluation of a novel delayed-type hypersensitivity assay toCandida albicansin adult and neonatal rats

Helminth Antigens Enable CpG-Activated Dendritic Cells to Inhibit the Symptoms of Collagen-induced Arthritis through Foxp3+ Regulatory T Cells

Wound dressings loaded with an anti-inflammatory jucá (Libidibia ferrea) extract using supercritical carbon dioxide technology

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Chitosan‐induced phospholipase A₂ activation and arachidonic acid mobilization in P388D₁ macrophages