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Airway responsiveness after acute exposure to urban particulate matter 1648 in a DO11.10 murine model

¹Department of Pharmaceutical Science, Center for Environmental Health Sciences, University of Montana, Missoula, Montana 59812; and ²Department of Pediatrics, University of Texas Houston Health Sciences Center, Houston, Texas 77030

Submitted 24 June 2003 ; accepted in final form 21 October 2003

Enhanced airway responsiveness (AR) is a well-established characteristic of asthma that epidemiological evidence has linked with inhalation of ambient particulate matter (PM). To determine whether acute exposure to urban particulate matter PM1648 can exacerbate airway responsiveness and alter the early inflammatory state, a unique murine model was created using DO11.10 mice, transgenic for a T cell receptor recognizing ovalbumin_323-339. Because these mice are sensitive to ovalbumin, immunization procedures involving adjuvant or long aerosolization procedures are not necessary and, therefore, allow for the study of an acute AR response to particulate and antigen in young animals. AR was assessed by barometric whole body plethysmography and measured by enhanced pause (Penh). PM1648 and ovalbumin were administered intranasally 72 and 4 h before to AR assessment, respectively. A dose-response relationship between PM1648 and Penh was determined, and doses at or above 500 µg had Penh values significantly higher than saline controls. Penh values of control particle titanium dioxide (TiO₂) were similar to saline controls demonstrating no nonspecific particulate effect on AR. Lung lavage at time of AR assessment showed no significant inflammation due to particulate exposure or ovalbumin alone; however, PM1648/ovalbumin and TiO₂/ovalbumin combinations resulted in significant neutrophilia. In addition, treatment with polymyxin B to remove surface-bound endotoxin did not significantly affect Penh levels. These results indicate that PM1648 specifically increases AR in a dose-dependent manner and that this exacerbation is not a direct response to increased neutrophil concentration, particle-bound endotoxin or nonspecific particle effects.

whole body plethysmography; ovalbumin; enhanced pause; neutrophilia