BLOCKADE OF CD49D (ALPHA(4) INTEGRIN) ON INTRAPULMONARY BUT NOT CIRCULATING LEUKOCYTES INHIBITS AIRWAY INFLAMMATION AND HYPERRESPONSIVENESSIN A MOUSE MODEL OF ASTHMA

Immunized mice after inhalation of specific antigen have the following characteristic features of human asthma: airway eosinophilia, mucus a nd Th2 cytokine release, and hyperresponsiveness to methacholine. A mo del of late-phase allergic pulmonary inflammation in ovalbumin-sensiti zed mice was used to address the role of the alpha(4) 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 o n circulating leukocytes by intraperitoneal CD49d mAb treatment only p revented the airway eosinophilia. In this asthma model, a CD49d-positi ve intrapulmonary leukocyte distinct from the eosinophil is the key ef fector cell of allergen-induced pulmonary inflammation and hyperrespon siveness.