E‐NTPDase1 and alkaline phosphatase control chemotaxis of human neutrophils by generating adenosine from released ATP
Abstract
Human polymorphonuclear neutrophils (PMN) release ATP in response to stimulation by chemoattractants. Released ATP and its product adenosine regulate chemotaxis by activating P2 and P1 receptors, respectively. Here we investigated the ecto‐ATPases that generate adenosine from released ATP. We find that ecto‐nucleoside‐triphosphate‐diphosphohydrolases 1 (E‐NTPDase1, CD39), which hydrolyses ATP to AMP, and alkaline phosphatase (ALP), which converts AMP to adenosine, are highly expressed in human PMN and that E‐NTPDase1 and ALP are recruited to the leading edge upon polarization of PMN in a chemotactic gradient. While E‐NTPDase1 is tightly associated with the leading edge, ALP remains more broadly distributed across the cell membrane. Inhibitors of E‐NTPDase1 reduced ATP hydrolysis by 60%, while inhibitors of ALP completely blocked the generation of adenosine. Inhibition of both enzymes significantly reduced the migration speed of PMN towards chemoattractant in a gradient field. Thus, E‐NTPDase1 and ALP play important roles in the control of PMN chemotaxis by generating extracellular adenosine from released ATP. (Supported by grants from NIGMS and DOD)
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2008
- Source ID
- 10.1096/fasebj.22.1_supplement.1179.3
Entities
People
- Paul A. Insel
- Ross Corriden
- Wolfgang G. Junger
- Yu Chen
Organizations
- Harvard University
- National Institute of General Medical Sciences
- United States Department of Defense
- University of California, San Diego