Labeling and exocytosis of secretory compartments in RBL mastocytes by polystyrene and mesoporous silica nanoparticles

Abstract

Background: For a safe 'in vivo' biomedical utilization of nanoparticles, it is essential to assess not only biocompatibility, but also the potential to trigger unwanted side effects at both cellular and tissue levels. Mastocytes (cells having secretory granules containing cytokines, vasoactive amine, and proteases) play a pivotal role in the immune and inflammatory responses against exogenous toxins. Mastocytes are also recruited in the tumor stroma and are involved in tumor vascularization and growth. Aim and methods: In this work, mastocyte-like rat basophilic leukemia (RBL) cells were used to investigate whether carboxyl-modified 30 nm polystyrene (PS) nanoparticles (NPs) and naked mesoporous silica (MPS) 10 nm NPs are able to label the secretory inflammatory granules, and possibly induce exocytosis of these granules. Uptake, cellular retention and localization of fluorescent NPs were analyzed by cytofluorometry and microscope imaging. Results: Our findings were that: (1) secretory granules of mastocytes are accessible by NPs via endocytosis; (2) PS and MPS silica NPs label two distinct subpopulations of inflammatory granules in RBL mastocytes; and (3) PS NPs induce calcium-dependent exocytosis of inflammatory granules. Conclusion: These findings highlight the value of NPs for live imaging of inflammatory processes, and also have important implications for the clinical use of PS-based NPs, due to their potential to trigger the unwanted activation of mastocytes.

Cellular Targets and Mechanisms in the Cytotoxic Action of Non-biodegradable Engineered Nanoparticles

“…Later, it was realized that also engineered NPs, TiO 2 and polystyrene NPs, increase intracellular Ca 2+ concentrations by binding to Ca 2+ channels, while ZnO increased intracellular Ca 2+ concentrations by a combination on membrane damage, channel interaction, and Ca 2+ release from intracellular stores [49]. Activation of these channels appears, for instance, to be involved in the exocytosis of pro-inflammatory secretory granules from rat mastocytes by polystyrene particles [50]. In addition to interference with Ca 2+ signaling, 20 nm polystyrene NPs can activate K + channels and cystic fibrosis transmembrane conductance regulator Cl − channels [49c] and quantum dots impair functional properties of sodium channels in hippocampal neurons [51].…”

Contribution of engineered nanomaterials physicochemical properties to mast cell degranulation

“…Studying adverse immune responses following ENM exposure has become increasingly important with emergence of nanomedicines, considering drug allergies are a limiting factor for patient compliance and could often lead to drug removal from the market 16 . Mast cells, involved in the innate and adaptive immune responses functioning in host defense, have been implicated as an early effector cell in response to ENM exposures 17 18 19 20 21 22 23 24 25 26 27 . They play a predominant role in the development of allergic inflammation, resulting in diseases such as allergies, asthma, and anaphylaxis.…”

Autophagy-dependent toxicity of amino-functionalized nanoparticles in ovarian cancer cells

“…57,58 In addition, the availability of charged PS-NPs embedded with a fluorescent probe makes these NPs a valid tool for monitoring the uptake and toxicity at the cellular level. [15][16][17][59][60][61] Thus, PS-NPs can be used as a paradigm for in vitro investigation of Fig. 9 Inhibition of mitochondrial ROS production by resveratrol restores ATG4-mediated autophagy and prevents cell death in OAW42 cells exposed to NH 2 -PS-NPs.…”

“…12,13 Besides, the biological effects vary among the cell types. 14 The biological responses to NPs include prompt extrusion, 12,15,16 re-localization in other compartments, [16][17][18][19] production of ROS, 20,21 cell cycle arrest, 22,23 cell death and autophagy. [24][25][26][27][28] The role of autophagy and the cellular and molecular mechanisms involved in the toxicity elicited in vivo and in vitro by NPs of different size, charge and material have recently been reviewed.…”