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Purinergic P2X7 Receptor: A Pivotal Role in Surfactant Regulation?
Author(s) -
MISHRA AMARJIT,
CHINTAGARI NARENDRANATH REDDY,
LIU LIN
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.931.4
Subject(s) - apyrase , secretion , purinergic receptor , paracrine signalling , pulmonary surfactant , p2y receptor , angiotensin ii receptor type 1 , microbiology and biotechnology , receptor , purinergic signalling , chemistry , autocrine signalling , medicine , endocrinology , agonist , angiotensin ii , biology , adenosine receptor , biochemistry
P2X7 receptors (P2X7R) are specifically expressed in lung alveolar type I cells (AT1). We hypothesize that the activation of P2X7R on AT1 cells releases ATP and stimulates surfactant secretion from alveolar type II cells (AT2) via a paracrine manner. To test this hypothesis, we isolated primary rat alveolar epithelial cells by releasing them from lung tissues using enzymatic digestion. Immunophenotyping and cytometric analysis with cell specific markers showed 32% and 64% AT1 and AT2, respectively. Surfactant lipid secretion was measured on overnight cultured AT1 and AT2 cells in presence of 3′‐O‐(4‐benzoyl) benzoyl adenosine 5′‐triphosphate (BzATP), a known potent P2X7R agonist. BzATP significantly increased surfactant lipid secretion in the mixed cells in a dose dependent manner when compared to AT2 cells cultured alone and was significantly inhibited by P2X7R antagonist, Brilliant Blue G (BBG). However, when ATP was scavenged with apyrase and ADA, BzATP evoked surfactant secretion was significantly decreased. BzATP‐mediated secretion was also reduced in the presence of suramin and staurosporine, indicating the possible involvement of P2Y2R and downstream PKC‐mediated signaling pathway. Our results suggest that AT1 communicate in a paracrine fashion with AT2 cells in modulating surfactant secretion via P2X7R activation and ATP release.[NIH; HL 052146]