Dose response relationship between the chemical composition of 2.4 micrometer particles and human lung cells (A549) cytokine expression

Inhalation of ambient particulate matter is a factor in the pathogenesis of cardiovascular and pulmonary diseases. A goal of this thesis was to identify specific chemical components of particulate matter most significant in its causing adverse health effects. To address this issue, instrumentation and methodology were developed with which one could design, create, levitate and deposit 2.4±0.1 mm diameter particles of known chemical composition onto lung cells, in vitro, followed by the monitoring of downstream human lung cell (A549) response. An outcome of the method development process was an investigation of two disparate components hypothesized to be significant factors in particulate matter toxicity, endotoxin and soluble metals. The effect of incorporating these components, separately, into carbon particles on cytokine expression from lung cells was measured. Through immunocytochemistry studies of the expression of intercellular adhesion molecule (ICAM)-1, it was learned that endotoxin and metal salt both effect its upregulation and their relative toxicity were determined to be 9.0×10-5 versus 4.4×10-3 per particle number per pg of LPS and Zn, respectively. Additionally, another biomolecule not yet identified but observed using MALDI-TOF-MS (m/z= 8.3 kDa) was upregulated by A549 cells incubated with these particle types.