Airway responsiveness after acute exposure to urban particulate matter 1648 in a DO11.10 murine model.
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 microg had Penh values significantly higher than saline controls. Penh values of control particle titanium dioxide (TiO(2)) 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 TiO(2)/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.
Archer
Amy J
AJ
Center for Environmental Health Sciences, Department of Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA.
Cramton
Jennifer L H
JL
Pfau
Jean C
JC
Colasurdo
Giuseppe
G
Holian
Andrij
A
D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*
D000393:Air Pollutants; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D010047:Ovalbumin