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ATP induces alveolar/capillary cross talk in the lung
Author(s) -
Kiefmann Rainer,
Parthasarathi Kaushik,
Lindert Jens,
Bhattacharya Jahar
Publication year - 2006
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.20.5.lb40-b
Subject(s) - purinergic receptor , apyrase , paracrine signalling , chemistry , alveolar epithelium , lung , microbiology and biotechnology , receptor , medicine , biology , biochemistry
ATP released from lung epithelial cells e.g. following mechanical ventilation mediates alveolar inflammatory responses. To determine mechanisms we considered an ATP‐induced signaling from alveoli to capillaries. We blood‐perfused (14 ml/min) isolated rat lungs at constant arterial, venous and alveolar pressures (Palv) of 10, 3 and 5 cmH2O, respectively (n=4). We quantified cytosolic Ca2+ (Ca2+cyt) in single epithelial and endothelial cells by real‐time imaging of fura 2 using epifluorescence microscopy. Under baseline conditions, Ca2+cyt oscillated in epithelial cells with an amplitude of 14±4 nM and in endothelial cells of 9±1 nM. An intra‐alveolar infusion of 100 μM ATP increased the oscillation amplitude to 36±6 nM in epithelial cells and to 18±2 nM in epithelial cells (P<0.05). Both, the intra‐alveolar microinfusion of the purinergic receptor antagonist, PPADS (100 μM), and the nucleotide hydrolyzing enzyme, apyrase (50 U/ml), completely blocked the alveolar ATP‐induced Ca2+cyt. We interpret that alveolar ATP‐induced epithelial Ca2+cyt oscillations causes a paracrine signaling to adjacent capillaries followed by endothelial Ca2+cyt oscillations. This ATP‐induced alveolar/capillary cross talk may be relevant in high‐tidal volume mechanical ventilation associated lung injury (supported by HL57556, HL69514).