Release of adenosine triphosphate by adenosine diphosphate in whole blood and in erythrocyte suspensions

Abstract

In whole blood samples from thrombocytopenic patients, large amounts of ATP were released by ADP, exceeding the level obtained with samples from normal persons by far. Because we suspected that the high potential of ATP in erythrocytes would be the main source for this phenomenon, the release of ATP by ADP was measured in whole blood samples from normal, thrombocytopenic, and leukocytopenic persons and in suspensions of washed erythrocytes. The release was recorded by a Whole Blood Lumi-Aggregometer type 500 VS (Chrono-Log Corporation, Havertown, PA) using the luciferin-luciferase system. Not only in samples from thrombocytopenic persons but also with normal platelet count, increasing amounts of ATP were released with increasing ADP concentrations, finally exceeding the ATP releasable from thrombocytes by thrombin. The amounts of ADP required to match the ATP release of thrombin were closely correlated with the platelet counts in the samples. With lower platelet counts, the release mechanism from erythrocytes could be stimulated more easily by low concentrations of ADP. The binding of ADP to platelets occurred with ostensibly higher affinity. The phenomenon of overshooting ATP release was also observed in samples from extremely leukocytopenic patients. A very large release of ATP was also achieved in suspensions of washed erythrocytes. In this way our hypothesis of ATP release from erythrocytes by ADP was confirmed again. The mechanism of the release from erythrocytes remains unclear. We speculate that its purpose is to regulate extracellular nucleotides in the circulating blood.

Temporal Interleukin-1β Secretion from Primary Human Peripheral Blood Monocytes by P2X7-independent and P2X7-dependent Mechanisms

“…These data suggest the existence of a release mechanism of IL-1β that has two points of regulation: an initial phase of IL-1β release rapidly amplified by ATP signaling potentially providing monocytes with an ability to regulate inflammation in a graded manner, in which contact with pathogens would initiate IL-1β production, and an accentuated release to rapidly amplify local effects, perhaps reflecting tissue damage or platelet activation (both good sources of ATP (47, 48)). The phenotypes of responses between donors to TLR agonists (with or without BzATP) for both monocytes and MDM were robust in all experiments.…”

Ca2+-independent PLA2 controls endothelial store-operated Ca2+ entry and vascular tone in intact aorta

“…Therefore, these results suggest that the iPLA 2 -dependent stimulation of endothelial store-operated Ca 2ϩ entry represents a physiological mechanism by which circulating ATP could modulate the aortic tone. This may be particularly relevant in the case of an increased blood ATP concentration, a phenomenon that can happen in injurious situations like hypoxia or in diseases where ATP is released from red blood cells (11,12,19,22).…”

Purinoceptors are involved in the induction of an osmolyte permeability in malaria‐infected and oxidized human erythrocytes

“…This release is possibly accomplished by an ATP release pathway suggesting a positive feedback of the ATP‐induced signaling cascade (ATP release simply by hemolysis of infected or oxidized RBCs, however, cannot be excluded). ATP (ADP)‐induced ATP release has been demonstrated in human RBCs (36, 37).…”