Steroid inhibition of erythrocyte-derived ATP reduces endothelial cell production of nitric oxide in a 3D-printed fluidic model

Abstract

Multiple sclerosis (MS) is a disease of the central nervous system affecting over 2.5 million people worldwide.

Interferon-β Decreases the Hypermetabolic State of Red Blood Cells from Patients with Multiple Sclerosis

“…In the United States, autoimmune diseases affect 41 million people, with an estimated 1 million living with multiple sclerosis (MS) . Worldwide, approximately 2.8 million people have a diagnosis of MS, , a progressive disease in which the myelin sheath surrounding axons in the central nervous system (CNS) becomes damaged − resulting in lesion formation and altered nerve signaling. ,, An exact mechanism leading to myelin sheath damage is not known, although a breach in the blood brain barrier (BBB), which normally limits diffusion of molecules into the CNS, has been thought to be a possible determinant in sheath damage . Alterations in the BBB have been reported in people with MS and are reported to contribute to physical and cognitive decline .…”

“…Alterations in the BBB have been reported in people with MS and are reported to contribute to physical and cognitive decline . While the mechanism of destruction of the myelin sheath and onset of MS is unknown, there are possible molecular suspects that have been reported to be higher in MS tissues and plasma in comparison to controls, including nitric oxide (NO). ,,− …”

A 3D-printed, multi-modal microfluidic device for measuring nitric oxide and ATP release from flowing red blood cells

“…This type of robust device opens new possibilities for studying NO and ATP interdependence, especially in diseased RBCs since in autoimmune diseases, patients are found to have abnormal levels or behavior in terms of NO and ATP. [70][71][72][73] This multi-modal device has the potential to study any electrochemically active analyte and could be paired with cell culture to study cell-to-cell interactions, for example, how hypoxic RBCs stimulate endothelial cells and the interplay between RBCs and endothelial cells on NO production.…”

Red blood cells in type 1 diabetes and multiple sclerosis and technologies to measure their emerging roles

“…Lower RBC deformability in MS patients compared to healthy controls was surprising because decreased deformability has been shown to decrease ATP and subsequent NO (in which MS patients demonstrate increased levels). Patients in the studies by Simpson et al were receiving steroids, which decreases deformability [ 26 , 32 ]. The decrease in deformability in Janes' studies could be due to the variation in RBC diameter between MS and control RBCs.…”

“…A table summarizing red blood cell, adenosine triphosphate (ATP), and nitric oxide (NO) characteristics in various autoimmune diseases. Autoimmune Disease Characteristics Type 1 Diabetes Decreased RBC-derived ATP release [ [7] , [8] , [9] ] Altered eNOS function and decreased NO release [ 8 , [10] , [11] , [12] , [13] , [14] ] Reduced RBC deformability [ [15] , [16] , [17] , [18] , [19] , [20] ] Multiple Sclerosis Increased levels of NO [ [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] ] Increased RBC-derived ATP release [ 26 , 29 ] Debated RBC deformability [ [30] , [31] , [32] , [33] ] Alzheimer's Disease Reduced RBC-derived ATP release [ [34] , [35] , [36] , [37] ] …”