Hypocontractile airway smooth muscle phenotype exhibits enhanced β2 laminin chain expression in lung allergy model.

Abstract

Sensitization with ovalbumin (OVA) in guinea pigs to induce anti-OVA IgE generates various allergic response phenotypes. One phenotype, characterized by the absence of bronchial obstruction and airway hyperresponsiveness in response to chronic antigen challenge, is termed non-responding (NR) and exhibits high IFN-γ levels. The Th1 cytokine profile is linked with high laminin β2 expression. This study evaluated laminin β2 expression in the chronic NR phenotype. Guinea pigs were sensitized and challenged with OVA three times (acute) or twelve times (chronic). Guinea pigs that responded to all challenges formed the asthma model phenotype. Controls were sensitized and challenged with saline. Immunohistochemistry was used to observe laminin β2 and its receptor, the α6 integrin subunit, in bronchial and arterial intrapulmonary smooth muscles. Only chronic NR guinea pigs showed increased laminin β2 expression in these muscles, while it remained similar in other groups. The α6 integrin subunit significantly increased in the acute and chronic asthma models, chronic controls, and NR guinea pigs in bronchial smooth muscle. In arterial intrapulmonary smooth muscle, the α6 integrin subunit increased in acute NR and chronic asthma model guinea pigs. The expression of laminin β2 in bronchial and arterial intrapulmonary smooth muscles correlates with α6 integrin subunit levels, and higher levels of laminin β2 were significantly related to reduced antigen-induced bronchial obstruction and reactivity to histamine. The expression of these proteins does not affect the proliferation of pulmonary blood vessels. Laminin β2 chain overexpression is likely involved in the chronic containment of the obstructive allergic response.