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1.
Front Immunol ; 10: 138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30833944

RESUMO

Mast cells (MC) are important immune sentinels found in most tissue and widely recognized for their role as mediators of Type I hypersensitivity. However, they also secrete anti-cancer mediators such as tumor necrosis factor alpha (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The purpose of this study was to investigate adipose tissue as a new source of MC in quantities that could be used to study MC biology focusing on their ability to bind to and kill breast cancer cells. We tested several cell culture media previously demonstrated to induce MC differentiation. We report here the generation of functional human MC from adipose tissue. The adipose-derived mast cells (ADMC) are phenotypically and functionally similar to connective tissue expressing tryptase, chymase, c-kit, and FcεRI and capable of degranulating after cross-linking of FcεRI. The ADMC, sensitized with anti-HER2/neu IgE antibodies with human constant regions (trastuzumab IgE and/or C6MH3-B1 IgE), bound to and released MC mediators when incubated with HER2/neu-positive human breast cancer cells (SK-BR-3 and BT-474). Importantly, the HER2/neu IgE-sensitized ADMC induced breast cancer cell (SK-BR-3) death through apoptosis. Breast cancer cell apoptosis was observed after the addition of cell-free supernatants containing mediators released from FcεRI-challenged ADMC. Apoptosis was significantly reduced when TNF-α blocking antibodies were added to the media. Adipose tissue represents a source MC that could be used for multiple research purposes and potentially as a cell-mediated cancer immunotherapy through the expansion of autologous (or allogeneic) MC that can be targeted to tumors through IgE antibodies recognizing tumor specific antigens.


Assuntos
Tecido Adiposo/citologia , Neoplasias da Mama , Mastócitos/imunologia , Apoptose , Células Cultivadas , Citotoxicidade Imunológica , Humanos
2.
Nanomedicine ; 13(6): 2037-2048, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28457935

RESUMO

The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbol myristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology.Lipoprotein-induced generation of TNF-α, C5a-induced MC activation, ICAM-1 driven adhesion, and CD36 expression were significantly inhibited in FD treated cells compared to non-treated cells. Inhibition appeared to be mediated through the NF-κB pathway as FD reduced expression of NF-κB and atherosclerosis-associated genes. Compared to controls, FD dramatically inhibited plaque formation in arteries of apolipoprotein E null mice. Thus, FD may be an unrecognized therapy to prevent atherosclerotic lesions via inhibition of foam cell formation and MC stabilization.


Assuntos
Células Espumosas/efeitos dos fármacos , Fulerenos/farmacologia , Mastócitos/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Placa Aterosclerótica/prevenção & controle , Animais , Células Cultivadas , Células Espumosas/metabolismo , Células Espumosas/patologia , Humanos , Masculino , Mastócitos/metabolismo , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Células U937
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