Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. A new approach to platelet activation and recruitment.

Abstract

Erythrocytes are known to influence hemostasis. Bleeding times are prolonged in anemia and corrected by normalizing the hematocrit. We now demonstrate that intact erythrocytes modulate biochemical and functional responsiveness of activated platelets. A two-stage procedure, permitting studies of cell-cell interactions and independently evaluating platelet activation and recruitment within 1 min of stimulation, was developed. Erythrocytes increased platelet serotonin release despite aspirin treatment, enzymatic adenosine diphosphate removal, protease inhibition, or combinations thereof. The data suggested that erythrocyte enhancement of platelet reactivity can reduce the therapeutic effectiveness of aspirin.Erythrocytes metabolically modified platelet arachidonate or eicosapentaenoate release and eicosanoid formation. They promoted significant increases in cyclooxygenase and lipoxygenase metabolites upon platelet stimulation with collagen or thrombin. However, with ionophore, erythrocytes strongly reduced platelet lipoxygenation. These erythrocyte modulatory effects were stimulus-specific. Activated platelet-erythrocyte mixtures, with or without aspirin, promoted 3-10-fold increases in extracellular free fatty acid, which would be available for transcellular metabolism. Erythrocyte-induced increases in free eicosapentaenoate may contribute to antithrombotic and anti-inflammatory effects of this fish oil derivative.

Cell-Free and Erythrocytic S -Nitrosohemoglobin Inhibits Human Platelet Aggregation

“…Erythrocytes markedly enhance the platelet release reaction, eicosanoid biosynthesis, and platelet recruitment, 20,21 effects that can be attenuated in human volunteers by daily ingestion of aspirin. 22 RBCs are also rich sources of ADP, the spontaneous and/or evoked release of which has powerful platelet-activating effects in vitro.…”

Erythrocyte Alterations and Increased Cardiovascular Risk in Chronic Renal Failure

“…Interactions between platelets and erythrocytes can markedly enhance in vitro several aspects of platelet reactivity (80,81), and may be implicated in vivo in vascular abnormalities found in sickle cell disease (76,77). Although atherosclerosis and vascular events are common in uremic patients, the significance of platelet-RBC aggregates in these patients remains yet to be elucidated.…”

PGE2 in the regulation of programmed erythrocyte death

“…25 Several lines of evidence indeed point to a role of erythrocytes in the regulation of hemostasis. [57][58][59][60] Beyond that, PGE 2 is a highly active mediator in inflammation, chemotactic processes, and cell damage (for review see Laufer 61 ). PGE 2 -dependent regulation of cation channels may also play a role in nucleated cells which similarly express cell volume regulatory cation channels.…”