Blockade of CD49d (alpha4 integrin) on intrapulmonary but not circulating leukocytes inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma.
Immunized mice after inhalation of specific antigen have the following characteristic features of human asthma: airway eosinophilia, mucus and Th2 cytokine release, and hyperresponsiveness to methacholine. A model of late-phase allergic pulmonary inflammation in ovalbumin-sensitized mice was used to address the role of the alpha4 integrin (CD49d) in mediating the airway inflammation and hyperresponsiveness. Local, intrapulmonary blockade of CD49d by intranasal administration of CD49d mAb inhibited all signs of lung inflammation, IL-4 and IL-5 release, and hyperresponsiveness to methacholine. In contrast, CD49d blockade on circulating leukocytes by intraperitoneal CD49d mAb treatment only prevented the airway eosinophilia. In this asthma model, a CD49d-positive intrapulmonary leukocyte distinct from the eosinophil is the key effector cell of allergen-induced pulmonary inflammation and hyperresponsiveness.
Henderson
W R
WR
Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
Chi
E Y
EY
Albert
R K
RK
Chu
S J
SJ
Lamm
W J
WJ
Rochon
Y
Y
Jonas
M
M
Christie
P E
PE
Harlan
J M
JM
D000485:Allergens; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002465:Cell Movement; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D039441:Integrin alpha4; D007962:Leukocytes / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D012130:Respiratory Hypersensitivity / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D000485:Allergens; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D039441:Integrin alpha4; D010047:Ovalbumin