Silencing Bruton's tyrosine kinase in alveolar neutrophils protects mice from LPS/immune complex-induced acute lung injury.

Autor:	Krupa A; 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;, Fol M; Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas; Department of Immunology and Infectious Biology, University of Lodz, Lodz, Poland., Rahman M; Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas;, Stokes KY; Department of Molecular and Cellular Physiology and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana;, Florence JM; Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas;, Leskov IL; Department of Molecular and Cellular Physiology and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana;, Khoretonenko MV; Department of Molecular and Cellular Physiology and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana;, Matthay MA; Departments of Medicine and Anesthesia, University of California, San Francisco, California; and., Liu KD; Departments of Medicine and Anesthesia, University of California, San Francisco, California; and., Calfee CS; Departments of Medicine and Anesthesia, University of California, San Francisco, California; and., Tvinnereim A; Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas;, Rosenfield GR; Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas;, Kurdowska AK; Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas; anna.kurdowska@uthct.edu.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2014 Sep 15; Vol. 307 (6), pp. L435-48. Date of Electronic Publication: 2014 Aug 01.
DOI:	10.1152/ajplung.00234.2013
Abstrakt:	Previous 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.)
Databáze:	MEDLINE
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