Neutrophils as sources of extracellular nucleotides: functional consequences at the vascular interface - PubMed (original) (raw)

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Neutrophils as sources of extracellular nucleotides: functional consequences at the vascular interface

Holger K Eltzschig et al. Trends Cardiovasc Med. 2008 Apr.

Abstract

Nucleotide signaling is currently an area of intense investigation. Extracellular adenosine triphosphate (ATP) liberated during hypoxia or inflammation can either signal directly to purinergic receptors or, after phosphohydrolytic metabolism, can activate surface adenosine receptors. Given the association of polymorphonuclear leukocytes (PMNs) with adenine nucleotide/nucleoside signaling in the inflammatory milieu, it was recently demonstrated that PMNs actively release ATP via a connexin 43 hemichannel-dependent mechanism. Here, we review the mechanisms of ATP release and subsequent functional implications of ATP metabolism at the interface between PMN and vascular endothelial cells during inflammation and in hypoxia.

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Figure 1

Figure 1

Model of PMN — endothelial crosstalk by extracellular nucleotides. At sites of hypoxia or ongoing inflammation, activated PMN provide an extracellular source of ATP through membrane Cx43 hemichannels. ATP released in this fashion is metabolized through two enzymatic steps and results in the liberation of extracellular adenosine. Adenosine generated through this pathway is available for activation of surface endothelial adenosine receptors, particularly the AdoA2BR. Diminished oxygen supply (hypoxia) at sites of inflammation coordinates the induction of CD39, CD73 and AdoA2BR. At such sites, post-receptor increases in intracellular cyclic AMP result in enhanced barrier function. This biochemical crosstalk mechanism may provide an innate mechanism to preserve vascular integrity and attenuate vascular leak. This model is adapted with permission from published work (Eltzschig et al. 2003).

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