The activation of bronchiolar clara cells and alveolar macrophage innate immunity prevents allergic inflammation of airways

GARCIA LUCIANA N; URIBE ECHEVARRÍA MARÍA ELISA; LEIMGRUBER CAROLINA; MALDONADO CRISTINA A

Los Cocos - Córdoba

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología

INNATE IMMUNE RESPONSE OF CLARA CELLS AND ALVEOLAR MACROPHAGES INDUCED BY LPS PREVENT ASTHMA DEVELOPMENT. GARCÍA LN*, URIBE ECHEVARRIA EM, LEIMGRUBER C, MALDONADO CA. Centro de Microscopía Electrónica- INICSA- CONICET. A possible reason for the increasing incidence of asthma is the lack of microbial stimulating signals of the modern lifestyle. It has been suggested that a response triggered by environmental endotoxins, such as the Escherichia Coli lipopolysacharide (LPS), through innate immune receptors like Toll- like receptors (TLR), may counterbalance the T helper (Th)-2 response of atopic asthma. Key component to lung innate immunity are Alveolar Macrophages (AM) and bronchiolar Clara Cells (CC), which secrete immunomodulatory proteins like CC16 and surfactant-D (SP-D) that modulate the allergic inflammation. However, both CC and AM, are affected by asthma. Accordingly, our aim was to examine if the pretreatment of CC and AM with LPS can prevent asthma development. We applied an asthma murine model developed in Balb/c adults female (n=12 per group) that were submitted to Ovoalbumin (OVA) (1mg/ml) intraperitoneal sensitization (day 0 and 14) followed by OVA (1mg/ml) daily intranasal challenges (day 24-33). A second group, LPSOVA, received intranasal LPS stimulus (10μg/50μl) previous (day -3 and -1) to OVA. ANOVA-Tukey test (p<0.05) was used for data statistical analysis. RESULTS: The morphological analysis showed profound changes in CC of LPSOVA versus OVA group, including reduced mucus metaplasia (p<0.001 AB-PAS technique), increased expression of CC16 and SP-D (p<0.05) by Western Blot, and of TNFα/TLR4 content by immonohistochemistry. Broncheoalveolar lavage (BAL) from LPSOVA group, showed increased levels of the Th1 related cytokines TNFα an IFNγ (p<0.001 versus OVA) and reduced the Th2 related-IL-4 levels and eosinophil number (p<0.01). In addition, AM isolated from BAL in LPSOVA showed a more effector profile, illustrated by increased expression of iNOS enzyme by immunofluorescence (p<0.001) and reduction of Arginasa-1 (p<0.01), an enzyme related to allergic inflammation. CONCLUSION: The pre-exposition to LPS-triggered innate immune response in CC and AM, which may be protective against asthma induced changes.