Superantigenic Activation of Human Cardiac Mast Cells.

Varricchi Varricchi,Borriello Borriello,Marone Marone,Spadaro Spadaro,Rivellese Rivellese,Pecoraro Pecoraro,Genovese Genovese,Loffredo Loffredo

doi:10.3390/ijms20081828

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.

Highlights

The term “superantigen” (SAg) refers to several proteins synthesized by a variety of bacteria and viruses that mimic, and exceed the activity of conventional antigens in activating T and B cells [1,2,3,4,5]
Four preparations of IgG (10−2 to 3 μg/mL) purified from the serum of normal donors did not cause histamine release. These results suggest that mast cells isolated from human heart express immunoglobulin E (IgE) bound to FcεRI
This study shows that primary mast cells isolated from human myocardial tissue can be activated by a human IgG anti-IgE isolated from the serum of a patient with atopic dermatitis

Summary

Introduction

The term “superantigen” (SAg) refers to several proteins synthesized by a variety of bacteria and viruses that mimic, and exceed the activity of conventional antigens in activating T and B cells [1,2,3,4,5]. Typical antigens are processed by antigen-presenting cells (APCs) into small peptides that bind a distal groove in the molecules of the major histocompatibility complex (MHC) [6]. The peptide: MHC (p:MHC) complex on the APC surface acts as a ligand of both T cell receptor (TCR) α and TCR β variable domains on a few specific T cell clones. SAgs bind directly to the lateral surfaces of the MHC class II molecules and to the Vβ domain of the TCR and bypass the processing and presentation of conventional antigens by APCs [7,8,9,10]. Conventional antigens stimulate less than 1 in 10,000–100,000 T cells, while SAgs can stimulate up to 20% of all T cells [1,3]. A wide range of diseases from autoimmune and allergic disorders, neoplasia, and immunodeficiencies can be associated with SAgs [11,12,13,14,15]

Methods

Results

Conclusion