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J Appl Physiol (December 12, 2003). doi:10.1152/japplphysiol.01128.2003
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Submitted on October 17, 2003
Accepted on December 5, 2003

Dust Mite-Induced Asthma in Cynomolgus Monkeys

Michael R Van Scott1*, Jerry L Hooker1, David Ehrmann1, Yoshimi Shibata1, Cynthia Kukoly2, Kenneth Salleng3, Gregory Westergaard4, Anthony Sandrasagra5, and Jonathan Nyce5

1 Physiology, East Carolina University, Greenville, NC, USA
2 Medicine, East Carolina University, Greenville, NC, USA
3 Comparative Medicine, East Carolina University, Greenville, NC, USA
4 LABS of Virginia, Yemmasee, SC, USA
5 EpiGenesis Pharmaceuticals, Inc., Cranbury, NJ, USA

* To whom correspondence should be addressed. E-mail: vanscottmi{at}mail.ecu.edu.

Animal models exhibiting high homology with humans at the genetic and pathophysiological levels will facilitate identification and validation of gene targets underlying asthma. In the present study, a nonhuman primate model of allergic asthma was developed by sensitizing cynomolgus monkeys to dust mite antigen. Sensitization elevated allergen-specific serum IgE and IgG levels, and peripheral blood mononuclear cells isolated from sensitized animals released IL-4, IL-5, and IL-10, but not IFN-{gamma}. Aerosolized allergen decreased dynamic compliance, and induced airway inflammation and hyperresponsiveness to aerosolized histamine. Albuterol and dexamethasone inhibited the airway constriction and inflammation induced by allergen, respectively. Airway wall remodeling which included goblet cell hyperplasia, basement membrane thickening, and smooth muscle hypertrophy was particularly evident in neonatally sensitized animals. In contrast to animals sensitized as adults, neonatally-sensitized animals exhibited increased sensitivity to adenosine and larger allergen-induced changes in airway resistance and dynamic compliance. These results demonstrate that sensitization of cynomolgus monkeys with dust mite induces asthma-like symptoms, some of which may be dependent on the age at the time of sensitization.




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