Dust mite-induced asthma in cynomolgus monkeys.
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 allergen-induced inflammation, respectively. Airway wall remodeling that 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 asthmalike symptoms, some of which may be dependent on age at the time of sensitization.
Van Scott
Michael R
MR
Department of Physiology, East Carolina University, Greenville, NC 27858, USA. vanscottmi@mail.ecu.edu
Hooker
Jerry L
JL
Ehrmann
David
D
Shibata
Yoshimi
Y
Kukoly
Cynthia
C
Salleng
Kenneth
K
Westergaard
Greg
G
Sandrasagra
Anthony
A
Nyce
Jonathan
J
D000241:Adenosine / Q000008:administration & dosage; D000336:Aerosols; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004391:Dust; D006632:Histamine / Q000008:administration & dosage; D006968:Hypersensitivity, Delayed / Q000503:physiopathology; D006969:Hypersensitivity, Immediate / Q000503:physiopathology; D007114:Immunization; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008168:Lung / Q000503:physiopathology; D008252:Macaca fascicularis; D008925:Mites / Q000276:immunology*; D012129:Respiratory Function Tests; D012130:Respiratory Hypersensitivity / Q000503:physiopathology; D012137:Respiratory System / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
D000336:Aerosols; D000485:Allergens; D016207:Cytokines; D004391:Dust; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D006632:Histamine; D000241:Adenosine