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Int. J. Mol. Sci. 2019, 20(8), 1828; https://doi.org/10.3390/ijms20081828

Superantigenic Activation of Human Cardiac Mast Cells

1
Department of Translational Medical Sciences, University of Naples Federico II, 80100 Naples, Italy
2
Center for Basic and Clinical Immunology Research (CISI), 80100 Naples, Italy
3
World Allergy Organization (WAO) Center of Excellence, 80100 Naples, Italy
4
Division of Gastroenterology, Boston Children’s Hospital and Harvard Medical School, Boston, 02115 MA, USA
5
Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, E1 4NS London, UK
6
Institute of Experimental Endocrinology and Oncology “Gaetano Salvatore”, National Research Council (CNR), 80100 Naples, Italy
*
Authors to whom correspondence should be addressed.
Received: 13 March 2019 / Revised: 9 April 2019 / Accepted: 10 April 2019 / Published: 12 April 2019
(This article belongs to the Special Issue Mechanisms of Inflammation in Degenerative Cardiovascular Conditions)
PDF [781 KB, uploaded 12 April 2019]

Abstract

B cell superantigens, also called immunoglobulin superantigens, bind to the variable regions of either the heavy or light chain of immunoglobulins mirroring the lymphocyte-activating properties of classical T cell superantigens. Protein A of Staphylococcus aureus, protein L of Peptostreptococcus magnus, and gp120 of HIV are typical immunoglobulin superantigens. Mast cells are immune cells expressing the high-affinity receptor for IgE (FcεRI) and are strategically located in the human heart, where they play a role in several cardiometabolic diseases. Here, we investigated whether immunoglobulin superantigens induced the activation of human heart mast cells (HHMCs). Protein A induced the de novo synthesis of cysteinyl leukotriene C4 (LTC4) from HHMCs through the interaction with IgE VH3+ bound to FcεRI. Protein L stimulated the production of prostaglandin D2 (PGD2) from HHMCs through the interaction with κ light chains of IgE. HIV glycoprotein gp120 induced the release of preformed (histamine) and de novo synthesized mediators, such as cysteinyl leukotriene C4 (LTC4), angiogenic (VEGF-A), and lymphangiogenic (VEGF-C) factors by interacting with the VH3 region of IgE. Collectively, our data indicate that bacterial and viral immunoglobulin superantigens can interact with different regions of IgE bound to FcεRI to induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from human cardiac mast cells.
Keywords: angiogenesis; heart; histamine; IgE; leukotriene C4; lymphangiogenesis; mast cells; myocardial infarction; prostaglandin D2; superantigens angiogenesis; heart; histamine; IgE; leukotriene C4; lymphangiogenesis; mast cells; myocardial infarction; prostaglandin D2; superantigens
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Varricchi, G.; Loffredo, S.; Borriello, F.; Pecoraro, A.; Rivellese, F.; Genovese, A.; Spadaro, G.; Marone, G. Superantigenic Activation of Human Cardiac Mast Cells. Int. J. Mol. Sci. 2019, 20, 1828.

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