Premium
Role of Purines in the Prevention of Acute Lung Injury (ALI)
Author(s) -
Siddaramappa Umapathy Nagavedi,
Gorshkov Boris,
Fan Zhenghong,
Verin Alexander Dmitriyevich
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.645.11
Subject(s) - adenosine , chemistry , evans blue , microbiology and biotechnology , in vivo , adenosine triphosphate , pharmacology , biochemistry , medicine , biology
ALI is a major cause of acute respiratory failure that is associated with high morbidity and mortality. Human pulmonary artery EC (HPAEC) expresses both P1 (Adenosine) and P2Y (ATP and ADP) receptors. We have already shown that ATP promotes EC barrier enhancementvia a complex cellsignaling and the involvement of specific trimeric G‐proteins with the association of both Gq and Gi (Circulaion Research, 2005,97,115–24). Recently, we showed the barrier enhancement property of Adenosine in HPAEC cells and specific siRNA studies showed the primary role of A2A in barrier enhancement. Both ATP and Adenosine are involved in the restoration of the microtubule disruption induced by Nocodazole as evidenced by ECIS (Electrical cell‐substrate impedance sensing) and Immunofluorescence. PPase1 inhibitor, Tautomycetin inhibited the ATP and Adenosine induced barrier enhancement in HPAEC cells which demonstrate the possible role of complex PPases pathway in barrier enhancement via ATP and Adenosine. In murine model of ALI, ATP administrated intravenously, attenuated inflammatory response by decreasing accumulation of cells (48%), and proteins (57%), in bronchioalveolar lavage (BAL), and by reducing neutrophil infiltration into alveoli. ATP reduced the LPS induced Evans Blue Dye (EBD) leakage from vascular space into BAL. In the similar murine model of ALI, Adenosine decreased the accumulation of protein (48%) into BAL. These novel findings strongly suggest that purinoreceptors stimulation exert a protective role against ALI, probably via decreasing endothelial junctional permeability in vitro and in vivo . Research Support, NHLBI;HL083327.