Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Anthony Dellinger

doi:10.4172/2157-7439.1000153

Abstract

Mast cells (MC) and peripheral blood basophils (PBB) are well known for their role in the allergic response mediated through high affinity IgE receptors (FceRI). However, these cells can also be stimulated by other non-allergic secretagogues to release their inflammatory mediators. Certain fullerene derivatives (FD) have already been shown to stabilize FceRI-mediated MC/PBB responses, but it is not know if they also stabilize these cells through non-IgEmediated mechanisms. A panel of FD was synthesized and tested for their ability to inhibit non-FceRI mediated release from human MC and PBB. It was found that specifically engineered FD could significantly inhibit calcium ionophore, compound 48/80, somatostatin, and poly L-lysine induced MC degranulation and cytokine production, as well as blunt degranulation and cytokine production from N-formyl-methionine-leucine-phenylalanine (fMLP), poly L-lysine, and calcium ionophore stimulated PBB. The mechanism of inhibition was due in part to the prevention of secretagogueinduced increases in cellular reactive oxygen species (ROS) and calcium levels as well as the reduced activation of the MAPK signaling intermediates ERK1/ERK2 and LAT. Additionally, preincubation of MC with FD blunted the prostaglandin D2 (PGD2) production upon exposure to inflammatory stimuli. In both cell types, the extent of inhibition of mediator release in response to each secretagogue was dependent on the moieties/side chains attached to the carbon cage. These results further extend the utility of fullerene nanomaterials to control mediator release through non-IgE mediated pathways in MC/PBB.

Highlights

Mast cells (MC) are ubiquitously expressed in almost all tissue and participate as effector cells for immune regulation
Recent studies suggest that water-soluble fullerene derivatives (FD) can inhibit FcεRI-induced MC responses in vitro, which translates to the prevention of MC-driven anaphylaxis and asthma in vivo [7,8,9]
Mast cells and Peripheral blood basophils (PBB) contribute to several disease processes through the release of inflammatory mediators through both IgE and non-IgE mechanisms

Summary

Introduction

Mast cells (MC) are ubiquitously expressed in almost all tissue and participate as effector cells for immune regulation. Recent studies suggest that water-soluble fullerene derivatives (FD) can inhibit FcεRI-induced MC responses in vitro, which translates to the prevention of MC-driven anaphylaxis and asthma in vivo [7,8,9]. It is clear certain FD can stabilize MC activation through FcεRI in vitro and in vivo it is not known if they can stabilize MC activation through non-FcεRI-mediated stimuli. It is demonstrated that FD inhibit non-IgE mediated pathways and the efficacy of FD relies on several factors: the active side chain moieties added to the fullerene cage, the type of cells evaluated, the secretagogue used to stimulate, and the pathway that is examined

Materials and Methods

Results

Discussion