Dose-response studies involving controlled deposition of less than 100 particles generated and levitated in an ac trap onto lung cells, in vitro, and quantitation of ICAM-1 differential expression.
A developing area of interest regarding the relationship between the adverse health effects associated with particles suspended in the troposphere is an understanding of how particle chemical composition influences different biological outcomes. Described is the development and application of an apparatus and methodology wherein a known number of particles of tropospherically relevant chemical composition can be designed and levitated in an alternating current (ac) trap followed by their controlled deposition directly from the ac trap onto air-liquid interface cultured lung cells. A downstream biological response, differential upregulation of intercellular adhesion molecule (ICAM)-1, was measurable using fluorescence microscopy in the air-liquid interface human lung cell cultures even though the dose per culture was 0-100 lipopolysaccharide (LPS)-containing elemental carbon particles (52 pg LPS per 6.3 microm diameter particle). Fluorescence emission intensity data measured from a 1 mm2 area centered over the site of particle deposition were fitted using a least squares linear regression line. Because the total mass of each different compound comprising each of the particles delivered to the culture was known, the data generated with this methodology can be expressed as a pro-inflammation potential (in this case ICAM-1 expression) per particle number and composition. Also described is how this methodology affords opportunities to quantitatively study pro-inflammatory intercellular signaling leading to ICAM-1 expression at sites distal to the site of particle deposition.
Haddrell
Allen E
AE
Department of Chemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, Canada V5A 1S6.
van Eeden
Stephen F
SF
Agnes
George R
GR
D000393:Air Pollutants / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000737:chemistry / Q000187:drug effects*; D010316:Particle Size; D012235:Rhodamines / Q000378:metabolism; D018675:Toxicity Tests / Q000295:instrumentation / Q000379:methods*
D000393:Air Pollutants; D008070:Lipopolysaccharides; D012235:Rhodamines; C026188:rhodamine 6G; D018799:Intercellular Adhesion Molecule-1