Alteration of pulmonary immunity to Listeria monocytogenes by diesel exhaust particles . I. Effects of DEPs on early pulmonary responses

Results

Pulmonary inflammatory responses to DEPs and Listeria. Intratracheal inoculation of 100,000 Listeria caused a significant increase in the number of lavageable neutrophils at 3 and 7 days postinfection compared with the noninfected controls. Significantly increased yield of lavageable AMs, however, was observed only at 7 days postinfection in these Listeria-infected animals (Table 1). Exposure to DEPs alone als0 resulted in significant increases in the number of AMs as well as in neutrophil infiltration. These alterations persisted through 7 days, and the magnitudes of change increased with increasing DEP exposure doses. At the higher DEP dose (100 mg/[m.sup.3]), the number of AMs and neutrophils in Listeria-infected rats were 2- and 4-7-fold that of the air and noninfected controls, respectively. The yield of BAL neutrophils from rats exposed to 100 mg/[m.sup.3] DEPs and Listeria was significantly higher than those from rats treated with either DEPs or Listeria alone.

As indices of lung injury, albumin content and LDH activity were measured in the acellular BAL fluid (Table 2). Exposure to DEPs alone did not increase BAL fluid albumin levels or LDH activity except at the higher dose and the 7-day postexposure time point. The results also show that Listeria infection alone caused increases in both albumin content and LDH activity compared with the noninfected control. In the high-dose DEP plus Listeria group, higher albumin levels and LDH activity were noted above Listeria alone at 3 days postexposure and for LDH at 7 days postexposure. There was, however, a descending trend in these elevations at day 7, suggesting that the lungs were recovering from the inflammatory injury.

Pulmonary clearance of Listeria. The effects of DEP exposure on lung clearance of Listeria are shown in Table 3. Rats exposed to dean air showed an increased bacterial count (from 1 x 105 to 4.3 x 105) in the lungs at day 3 but substantial bacterial clearance at day 7. In rats exposed to DEPs at 50 and 100 mg/[m.sup.3], the bacterial counts at day 3 were more than 2- and 10-fold that of the air control, respectively. Both increases were statistically significant. At day 7, the bacteria count for rats exposed to the higher dose of DEPs was much lower than that at day 3 but remained significantly elevated compared with air control.

Macrophage phagocytosis. The in vivo effects of DEP exposure and/or Listeria infection on the phagocytic activity of AMs are shown in Figure 1. These results indicate that at both 3 and 7 days postexposure, the WPI of AMs was significantly lowered as a result of DEP exposure in a dose-dependent manner. Listeria infection did not appear to alter the phagocytic activity of AMs from rats exposed to either clean air or DEPs. Figure 2 shows the dose- and time-dependent effects of DEPs on AM phagocytosis in vitro: the WPI of AMs decreases with increasing DEP dose and increasing incubation time. The cells treated with 100 pg/mL DEPs for 24 hr showed slightly decreased viability (79%), whereas the others showed no marked cytotoxicity after treatment with DEPs at the designed doses at each time point (viability ranging from 87% to 98%).