CONICET | Buscador de Institutos y Recursos Humanos

Asthma is a chronic Th2 inflammatory disorder of the airways. This allergic microenvironment induces Bronchiolar epithelial Clara cells (CCs) mucous metaplasia with loss of CCs specific protective mechanisms such as the secretion of CC16, an antiinflammatory protein, and Surfactant D (SP-D) with bactericide properties. On the other, allergy also influences on alveolar macrophages (AM), key players in the lung immune response, promoting their differentiation to M2 phenotype that contribute to remodelling in asthma. It has been proposed that stimulating innate immune mechanism (iim) with microbial compound may modulate the allergic Th2 inflammatory processes by inducing Th1-promoting cytokines. Thus, our aim was to evaluate the efficiency of promoting local innate immune activation by E. Coli lipopolysaccharide (LPS) to prevent the allergy-induced response. Female Balb/c mice (6-8week old) were assigned in groups. OVA group received primary and booster sensitization with i.p. injection of OVA adsorbed in alum on days 0 and 14. On days 24 to 34, airway challenge was performed with intranasal injection of 50 µl of 1% OVA solution. LPS-OVA group was pre-exposed with 50µl LPS before OVA (days -1 and -3). Controls for each group were challenged with OVA or LPS vehicle. 24hours after the last challenge, mice were sacrificed to obtain bronchoalveolar lavage (BAL) and lung tissue. Morphologic analysis and evaluation of the CCs defensive proteins and innate response markers were performed using Electron microscopy, immunochemistry, immunoblot, immunofluorescence and ELISA. Normal Clara cell phenotype was better preserved in LPS-OVA as judged by morphology and the higher CC16 and SP-D content (p