Purinergic P2X7 receptor regulates lung surfactant secretion in a paracrine manner

Amarjit Mishra, Narendranath Reddy Chintagari, Yujie Guo, Tingting Weng, Lijing Su, Lin Liu

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Alveolar epithelium is composed of alveolar epithelial cells of type I (AEC I) and type II (AEC II). AEC II secrete lung surfactant by means of exocytosis. P2X7 receptor (P2X7R), a P2 purinergic receptor, has been implicated in the regulation of synaptic transmission and inflammation. Here, we report that P2X7R, which is expressed in AEC I but not AEC II, is a novel mediator for the paracrine regulation of surfactant secretion in AEC II. In primary co-cultures of AEC I and AEC II benzoyl ATP (BzATP; an agonist of P2X7R) increased surfactant secretion, which was blocked by the P2X7R antagonist Brilliant Blue G. This effect was observed in AEC II cocultured with human embryonic kidney HEK-293 cells stably expressing rat P2X7R, but not when co-cultured with AEC I in which P2X7R was knocked down or in co-cultures of AEC I and AEC II isolated from P2X 7R-/- mice. BzATP-mediated secretion involved P2Y 2 receptor signaling because it was reduced by the addition of the ATP scavengers apyrase and adenosine deaminase and the P2Y2 receptor antagonist suramin. However, the stimulation with BzATP might also release other substances that potentially increase surfactant secretion as a greater stimulation of secretion was observed in AEC II incubated with BzATP when co-cultured with E10 or HEK-293-P2X7R cells than with ATP alone. P2X7R-/- mice failed to increase surfactant secretion in response to hyperventilation, pointing to the physiological relevance of P2X7R in maintaining surfactant homeostasis in the lung. These results suggest that the activation of P2X7R increases surfactant secretion by releasing ATP from AEC I and subsequently stimulating P2Y 2 receptors in AEC II.

Original languageEnglish (US)
Pages (from-to)657-668
Number of pages12
JournalJournal of cell science
Volume124
Issue number4
DOIs
StatePublished - Feb 15 2011

    Fingerprint

Keywords

  • Alveolar epithelial cells
  • Cell-cell communication
  • Exocytosis
  • P2X receptor

ASJC Scopus subject areas

  • Cell Biology

Cite this