Erythrocytes may synthesize their own nitric oxide

The ability of hemoglobin and myoglobin to bind nitric oxide (NO) produced by other cells and circulating vasodilators is well known. To characterize erythrocytes (RBCs), we used NADPH diaphorase labeling, as well as antibodies to the three known types of NO synthase (NOS 1, 2, and 3), and to a molecule usually associated with NOS, calmodulin. We show that the NADPH-diaphorase label labels myenteric neurons, endothelial cells, and the blood cells trapped in the lumen of the blood vessels running through the intestinal wall. The myenteric neurons are also positive for neuronal NOS (NOS1), calmodulin, and neuropeptide Y, indicating that they are NO-producing neurons. Endothelial cells are positive for NOS3 (a constitutive form of NOS), while macrophages and lymphocytes are positive for NOS2 (an inducible form of NOS). All are positive for calmodulin. Surprisingly, the RBCs are positive for NOS2 and 3, as well as calmodulin. Thus the RBCs possess all the cellular machinery to synthesize their own NO. We suggest that erythrocytes would synthesize and use NO to modulate their own physiology.