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ACTIVATION OF VANILLOID (VR1) RECEPTORS BY PARTICLE'S SURFACE CHARGE STIMULATES INFLAMMATORY CHANGES IN RESPIRATORY EPITHELIAL CELLS
Impact/Purpose:
This study was designed to address the relevance of a particle's electrostatic charge to initiating inflammation in respiratory epithelia.
Description:
Previous research from our laboratory indicates that particulate matter air pollutants carry an electronegative surface charge, the degree of which correlates with IL-6 release in human respiratory epithelial cells. This study was designed to test the theory that the positive surface charge resulting from a particle's inherent electro-negativity, is sufficient to stimulate vanilloid (VR1) receptors and biologically activate cells bearing those receptors. For this, nanometer sized synthetic polystyrene micro-spheres (SPM) charged with various functional groups (e.g., amino, sulfate, carboxyl) were obtained. When suspended in a neutral solution, these groups impart varying degrees of electronegativity to the polystyrene beads. Their zeta potentials (a reflection of their varying degrees of electronegativity) were measured in both cell culture media and distilled water. Human, immortalized bronchial-tracheal epithelial cells (i.e., BEAS-2B), were exposed to individual groups of SPM and tested for biological activation (i.e., membrane depolarization, [Ca2+]i, IL-6 release). BEAS-2B cells exposed to SPM carrying sulfate and carboxyl groups caused significant increases in [Ca2+]i, and IL-6 release. IL-6 release could be reduced by pretreatment with antagonists to acid sensitive pathways (i.e., amiloride) or to the VR1 receptor (i.e., capsazepine). The zeta potential, measured in cell culture nutrient medium and in distilled water, correlated with these biological changes. Cells exposed to these different SPM also stimulated increases in the mRNA-VR1 receptor and the mRNA-IL-6, transcripts. However, only those SPM with the highest electronegative zeta potentials stimulated mRNA-VR1 receptor. These data indicate that the surface charge alone, carried on an otherwise biologically inert substance, is sufficient to initiate measurable biological responses in human epithelial target cells that result in inflammatory changes.