TY - JOUR T1 - Blocking Focal adhesion kinase (FAK) protects against damage in a novel model of lymphocyte dominant lung injury JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.4469 VL - 56 IS - suppl 64 SP - 4469 AU - Danica Brister AU - Gurpreet Aulakah AU - Hong Zhang AU - Kamala Patel Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/4469.abstract N2 - Murine models help us understand human lung injuries by modeling the evolution of inflammation. Models of interstitial lung disease and hypersensitivity pneumonitis (HP) can identify targets to prevent fibrosis and preserve lung function.We present a novel mouse model of lymphocyte dominant lung injury as well as a therapeutic target for attenuating inflammation: focal adhesion kinase (FAK). Six-week, adjuvant-free intranasal ovalbumin (ova) sensitization and challenge increased leukocytes in bronchoalvolar lavage (BAL) fluid. Previous studies demonstrated Th2 responses to ova dominated by eosinophils, while our new model provoked a lymphocyte predominant response, similar to HP. Lung intravital microscopy showed severe vascular leakage with increased leukocyte trafficking. Histology and immunofluorescence showed airway thickening, increased mucus production and extensive B220+cell infiltration consistent with a sustained inflammatory response.FAK regulates leukocyte recruitment and affects lung fibrosis. A FAK inhibitor, PF-573228, was administered at the same time as ova during both the sensitization and challenge phases. We found that inhibiting FAK prevented leukocyte infiltration into the BAL and decreased production of pro-inflammatory cytokines. In summary, inhibition of FAK preserved lung architecture, prevented vascular leakage and limited leukocyte recruitment.Our data suggest that a chronic adjuvant-free ovalbumin model is useful for examining chronic lung inflammation in mice and that FAK plays a previously unrecognized role in regulating inflammation.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4469.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -