You are here:
GENETIC INFLUENCES ON IN VTIRO PARTICULATE MATTER-INDUCED AIRWAY EPITHELIAL INJURY AND INFLAMMATORY MEDIATOR RELEASE
Citation:
Dye, J A., J H. Richards, D L. Andrews, AND U P. Kodavanti. GENETIC INFLUENCES ON IN VTIRO PARTICULATE MATTER-INDUCED AIRWAY EPITHELIAL INJURY AND INFLAMMATORY MEDIATOR RELEASE. Presented at Society Symp. on Heterogeneity of the Airways" Form, Function, and Clinical Relevance", Boston, MA, October 3-6, 2002.
Description:
GENETIC INFLUENCES ON IN VITRO PARTICULATE MATTER-INDUCED AIRWAY EPITHELIAL INJURY AND INFLAMMATORY MEDIATOR RELEASE.
JA Dye, JH Richards, DA Andrews, UP Kodavanti. US EPA, RTP, NC, USA.
Particulate matter (PM) air pollution is capable of damaging the airway epithelium, facilitating induction of persistent airway inflammation and disease. Epidemiologic studies have demonstrated positive associations between ambient PM exposure and respiratory morbidity, most notably in individuals with pre-existing inflammatory airways disease or asthma. Limited in vitro evidence suggests that increased susceptibility of asthmatics to PM effects may relate, in part, to greater constitutive and PM-induced inflammatory mediator release from airway epithelial cells. In the present study, we investigated whether rodent airway epithelial response to PM would be similarly increased in cells derived from rat strains genetically predisposed to develop airway inflammation [i.e., spontaneously hypertensive (SH) and Brown-Norway (BN) rats]. To this end, pseudodifferentiated epithelial cultures were established from SH or BN rats, and healthy Sprague Dawley (CD) or WKY (background strain for SH) rats. Cytotoxicity data indicated that, compared to saline-exposed cells, exposure to PM #1 [a zinc-rich residual oil fly ash (ROFA) at 100 or 125 ?g/cm2 x 20 h] resulted in 1.9-to-3.1, 4.0-to-4.1, and 5.1-to-5.5-fold increases in LDH release in the CD-, WKY-, and SH-derived cells, respectively. Altered release of MIP-2, a potent neutrophil chemokine occurred, with decreases of 65% in CD-derived cells and increases of up to 48% in WKY- and 78% in SH-derived cells. Exposure to PM #2 (a vanadium-rich ROFA at 5 ?g/cm2 x 20 h) resulted in 1.6, 1.9-to-2.1, 2.1, and 3.3-to-3.9-fold increases in LDH release in CD-, WKY-, BN- and SH-derived cells. Correspondingly, MIP-2 release increased 1-to-1.8, 2.1-to-2.8, 6.0, and 5.5-to-13.3-fold. Similar trends were observed for IL-6 and TNF , with constitutive TNF production in BN cells only. In conclusion, there appears to be a strong genetic influence on airway epithelial responses elicited during in vitro exposure to emission source PM, the effects of which may relate to the enhanced in vivo susceptibility of these rodent strains to PM exposure.
(This abstract does not reflect US EPA policy).