Allergen induces the migration of platelets to lung tissue in allergic asthma

Rationale Platelets are essential for pulmonary leukocyte recruitment, airway hyperresponsiveness, and bronchial remodeling in animals with allergic inflammation and can be found in bronchoalveolar lavage of sensitized animals. No studies, however, have explored the direct migration of platelets to lungs. Objectives: To assess whether platelets migrate into lung parenchyma in response to inhaled allergen in ovalbumin-sensitized mice; to assess the role of the Fc epsilon RI receptor in this phenomenon; and to evaluate whether platelets from patients with asthma, or from sensitized mice, undergo chemotaxis in vitro in response to relevant antigens. Methods: Ovalbumin-sensitized wild-type (WT) mice, or FcR gamma-/mice lacking the FcERI gamma, were challenged with aerosolized allergen and lungs analyzed by platelet-specific immunohistochemistry. In some experiments, mice were depleted of platelets and cross-transfused with either WT or FcR gamma(-/-) platelets to assess the role of platelet FcR gamma(-/-). Chemotaxis of platelets from patients with asthma or from sensitized mice was studied in vitro. Measurements and Main Results: Histology of lungs revealed isolated platelets, migrating out of vessels and localizing underneath the airways after allergen challenge in WT but not in FcR gamma(-/-) mice. Platelets from patients with asthma and from sensitized WT mice, but not from sensitized FcR gamma(-/-) mice, migrated in vitro toward the relevant allergen or an anti-IgE. Platelets from normal mice were found to express Fc epsilon RI gamma and platelet-bound IgEs were increased in sensitized mice. Conclusions: Platelets migrate extravascularly in response to a sensitizing allergen via a mechanism dependent on the interaction among allergen, allergen-specific IgE, and the Fc epsilon RI, and this may allow them to participate directly in allergic tissue inflammation.