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Allergen Induces the Migration of Platelets to Lung Tissue in Allergic Asthma

¹ Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy; ² Pharmaceutical Sciences Research Division, Sackler Institute of Pulmonary Pharmacology, King's College London, London, United Kingdom; and ³ Respiratory Unit, Silvestrini Hospital, Perugia, Italy

Correspondence and requests for reprints should be addressed to Paolo Gresele, M.D., Ph.D., Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Via E. dal Pozzo, I-06126 Perugia, Italy. E-mail: grespa{at}unipg.it

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 FcRI 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^–/– mice lacking the FcRI, 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^–/– platelets to assess the role of platelet FcR^–/–. 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^–/– mice. Platelets from patients with asthma and from sensitized WT mice, but not from sensitized FcR^–/– mice, migrated in vitro toward the relevant allergen or an anti-IgE. Platelets from normal mice were found to express FcRI 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 FcRI, and this may allow them to participate directly in allergic tissue inflammation.

Key Words: allergen • chemotaxis • FcRI • IgE • inflammation • platelets

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Platelets are essential for pulmonary leukocyte recruitment, airway hyperresponsiveness, and airway wall remodeling in animal models of allergic inflammation. However, no studies have explored the direct migration of platelets in tissue. What This Study Adds to the Field We show that platelets are capable of directed migration both in vitro and in asthmatic lung.

 

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