You are here:
EFFECTS OF DIESEL EXHAUST ON PULMONARY RESPONSES DURING ALLERGIC SENSITIZATION TO AEROSOLIZED OVALBUMIN IN BALB/C MICE
Citation:
Singh, P., M. J. Daniels, D L. Andrews, E H. Boykin, Q T. Krantz, W P. Linak, AND M I. Gilmour. EFFECTS OF DIESEL EXHAUST ON PULMONARY RESPONSES DURING ALLERGIC SENSITIZATION TO AEROSOLIZED OVALBUMIN IN BALB/C MICE. Presented at Environ. Influences on Induction and Incidence of Asthma, RTP, NC, Oct. 18-19, 2004.
Description:
Effects of Diesel Exhaust on Pulmonary Responses During Allergic Sensitization to Aerosolized Ovalbumin in BALB/c Mice. P. Singh1, M.J. Daniels1, D. Andrews1, E. Boykin1, W. P. Linak2 and M.I. Gilmour1. 1USEPA, ORD, NHEERL, RTP, NC. 2 USEPA, ORD, NRMRL, RTP, NC.
Inhalation of diesel exhaust (DE) is associated with the development of asthma. Studies have also demonstrated that DE induces pulmonary changes that worsen asthmatic responses to respiratory allergens. We have established a DE inhalation-exposure system with the capability of adjusting from whole exhaust to gas-only exposures and that provides time-of-flight measurements of both size-fractioned particle concentrations and gaseous constituents such as NOX, SOX, O2, and CO2. In order to understand the effects of DE on early development of allergic airway responses in vivo, female BALB/c mice were exposed for 4 hours on a single day to either air or DE (particle concentrations of 0.2 mg/m3 and 2.0 mg/m3) or each day for 5 days followed by a daily 40 min exposure to aerosolized ovalbumin (OVA). Responses were measured in the bronchoalveolar lavage fluid (BALF) and in lung tissue homogenates on days 1 and 5. On day 1, DE exposed mice had increased inflammatory cell influx and raised levels of NFkB in lung tissues, which correlated with some increases in cytokine release, but no increases in cytotoxicity or pulmonary edema compared to air-exposed mice. Five days of DE exposure followed by OVA did not affect cellular inflammation, but cytotoxicity and pulmonary edema were increased compared to air/OVA exposures. Inhalation of OVA increased MIP-2 levels in the BALF and induced both NFkB and p38MAP kinase signaling proteins in lung cell lysates. Five days of DE exposure had a synergistic effect on lung injury in OVA sensitized mice but did not potentiate the cytokine response. We conclude that this system will be useful for tracking qualitative and kinetic changes in cellular responses during allergic sensitization with controlled modifications of inhalation exposure conditions. Further studies using this system will make it possible to correlate specific biological responses to individual particulate and gaseous components of DE emissions. (This abstract does not reflect EPA policy.)