Involvement of P2X4 receptor in P2X7 receptor-dependent cell death of mouse macrophages

Macrophages sense and kill bacteria through carbon monoxide–dependent inflammasome activation

“…Finally, to demonstrate a functional impact of the elevated ATP, macrophages were treated with exogenous ATP, which recapitulated that observed with CO in enhancing bacterial clearance (Figure 5F). Collectively, these data support a mechanism by which pathogens are recognized and destroyed by the host that involves activation of macrophages by ATP (54,55).…”

Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses

“…The co-expression of P2X4 receptors with P2X7 receptors was subsequently found to suppress P2X7-mediated autophagy and to facilitate the release of pro-inflammatory mediators in mouse macrophage RAW264.7 cells, consequently enhancing inflammation [108]. This association of P2X4 with P2X7 was also described in relation to macrophage cell death [109] but for which the underlying molecular mechanism is not yet unveiled. The effects by P2X7 receptor activation can also be tempered by E-NTPDase1 which degrades ATP at the cell surface of marcophages, potentially contributing to the fact that P2X7 is activated by higher concentrations of ATP compared with other P2 receptors [110].…”

The P2X7/P2X4 interaction shapes the purinergic response in murine macrophages

“…A C C E P T E D ACCEPTED MANUSCRIPT 11 Macrophages constitutively express P2X4R and P2X7R [15,16,22] and are a suitable cell type for investigating the physiological consequences of disrupting the P2X4/P2X7 interaction. Because YO-PRO-1 uptake, the release of IL-1β and cell death are triggered by P2X7R activation [8,19,27,28] we measured these responses in macrophages from P2X4-KO mice.…”

“…Yet non-conducting P2X4R changes the kinetics and magnitude of the ionic current through P2X7R [10,13,14] which is indicative of an agonisttriggered dynamic interaction. Because the inflammatory response and the cell death triggered after P2X7R activation are hindered by partial ablation of P2X4R in RAW264.7 macrophageswhich expresses both receptors [15][16][17]-we speculate that this interaction is physiologically relevant. Thus, in this work we studied the P2X7R/P2X4R interaction using coimmunoprecipitation, fluorescence resonance energy transfer and patch clamp techniques as well as the alterations of P2X7R-dependent physiological responses when P2X4R is absent.…”