Estudios de los macrófagos alveolares durante las reacciones alérgicas

Abstract

Airway allergy is induced after contact of allergens with the bronchial epithelium, triggering complex detrimental innate and adaptive immune responses, that in turn causes a series of pathological alterations of lung physiology, that can lead to asthma and ultimately to death by anaphylaxis. However, whether airway allergic/asthmatic reactions may cause pathological alterations of the alveolar system, and thus compromise respiratory gas exchange function, remains mostly unaddressed. In this work, we have described that house dust mite allergy caused a profound alveolar disorganization, involving the disappearance of alveolar macrophages (AMØs), pneumocyte hypertrophy, thickening of the alveolar lining and surfactant dysfunction. Allergic lung surfactant displayed a marked reduction in surfactant proteins SP-B and SP-C and a decreased efficiency to form surface-active films able to reach and maintain very low surface tensions, increasing the risk of atelectasis. The original population of AMØS was entirely replaced by new Ly6Chigh monocyte-derived AMØS, that persisted long after the resolution of allergy. Transition from monocytes to AMØs occurred through an intermediate pre-AMØS stage and was concomitant with the translocation into the alveolar space, Siglec-F upregulation, acquisition of autofluorescence and CX3CR1 downregulation. This study supports that asthma symptoms not only result from bronchiolar inflammation, but also from profound alterations in the alveolar system that lead to AMØ damage and surfactant dysfunction, compromising gas exchange.