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© The Rockefeller University Press,
0021-9525/2000//1349 $5.00
The Journal of Cell Biology, Volume 150, Number 6,
, 2000 1349-1360
Original Article |
Cell to Cell Communication in Response to Mechanical Stress via Bilateral Release of Atp and Utp in Polarized Epithelia
Airway epithelia are positioned at the interface between the body and the environment, and generate complex signaling responses to inhaled toxins and other stresses. Luminal mechanical stimulation of airway epithelial cells produces a propagating wave of elevated intracellular Ca2+ that coordinates components of the integrated epithelial stress response. In polarized airway epithelia, this response has been attributed to IP3 permeation through gap junctions. Using a combination of approaches, including enzymes that destroy extracellular nucleotides, purinergic receptor desensitization, and airway cells deficient in purinoceptors, we demonstrated that Ca2+ waves induced by luminal mechanical stimulation in polarized airway epithelia were initiated by the release of the 5' nucleotides, ATP and UTP, across both apical and basolateral membranes. The nucleotides released into the extracellular compartment interacted with purinoceptors at both membranes to trigger Ca2+ mobilization. Physiologically, apical membrane nucleotide-release coordinates airway mucociliary clearance responses (mucin and salt, water secretion, increased ciliary beat frequency), whereas basolateral release constitutes a paracrine mechanism by which mechanical stresses signal adjacent cells not only within the epithelium, but other cell types (nerves, inflammatory cells) in the submucosa. Nucleotide-release ipsilateral and contralateral to the surface stimulated constitutes a unique mechanism by which epithelia coordinate local and distant airway defense responses to mechanical stimuli.
Key Words: intercellular Ca2+ wave • nucleotide-release • airway epithelium • mechanical stimulus • P2-receptors
© 2000 The Rockefeller University Press
László Homolya's present address is Membrane Research Group of Hungarian Academy of Sciences, Budapest, H-1113, Hungary.Abbreviations used in this paper: [Ca2+]i, intracellular calcium concentration; CFTR, cystic fibrosis transmembrane conductance regulator; P2Y2-R (–/–), P2Y2-receptor deficient mice; PAPS, adenosine 3'-phosphate 5'-phosphosulfate; ROI, region of interest.
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