• Agnieszka Krupa, Marek Fol, Moshiur Rahman, Karen Y Stokes, Jon M Florence, Igor L Leskov, Mikhail V Khoretonenko, Michael A Matthay, Kathleen D Liu, Carolyn S Calfee, Amy Tvinnereim, Gabriel R Rosenfield, and Anna K Kurdowska.
• Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas; Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland;
• Am. J. Physiol. Lung Cell Mol. Physiol. 2014 Sep 15;307(6):L435-48.

AbstractPrevious observations made by our laboratory indicate that Bruton's tyrosine kinase (Btk) may play an important role in the pathophysiology of local inflammation in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). We have shown that there is cross talk between FcγRIIa and TLR4 in alveolar neutrophils from patients with ALI/ARDS and that Btk mediates the molecular cooperation between these two receptors. To study the function of Btk in vivo we have developed a unique two-hit model of ALI: LPS/immune complex (IC)-induced ALI. Furthermore, we conjugated F(ab)2 fragments of anti-neutrophil antibodies (Ly6G1A8) with specific siRNA for Btk to silence Btk specifically in alveolar neutrophils. It should be stressed that we are the first group to perform noninvasive transfections of neutrophils, both in vitro and in vivo. Importantly, our present findings indicate that silencing Btk in alveolar neutrophils has a dramatic protective effect in mice with LPS/IC-induced ALI, and that Btk regulates neutrophil survival and clearance of apoptotic neutrophils in this model. In conclusion, we put forward a hypothesis that Btk-targeted neutrophil specific therapy is a valid goal of research geared toward restoring homeostasis in lungs of patients with ALI/ARDS.Copyright © 2014 the American Physiological Society.

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