Purinergic P2x7 receptor: Pathophysiological role in alveolar functions

Abstract

Scope and Method of Study:

The present study was initiated to elucidate the role of P2X7 receptor in alveolar functions. P2X7 receptor function was studied in AEC I. P2X7 receptor stimulation in AEC I was examined for its role in ATP release and modulating the surfactant secretion from AEC II. Finally, we studied the novel function of P2X7 receptors in acute lung injury. We used a variety of techniques including cytokine array, ELISA, immunoblotting, histopathology to address the biological questions.

Findings and Conclusions:

1. P2X7 receptor are functional in AEC I. 2. Activation of P2X7 receptor in AEC I releases ATP. 3. P2X7 receptor stimulation in AEC I increases surfactant secretion from AEC II via paracrine release of ATP. 4. P2X7 receptor knock-out mice release less surfactant in response to hyperventilation. 5. P2X7 receptor antagonism and P2X7 receptor knock-out mice are less susceptible to acute lung injury. 6. The release of soluble VCAM-1 (sVCAM-1) from AEC I surface is P2X7 receptor-dependent. 7. Soluble VCAM-1 attracts neutrophils into the alveolar space in acute lung injury.