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Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.

Publication ,  Journal Article
McMahon, TJ; Shan, S; Riccio, DA; Batchvarova, M; Zhu, H; Telen, MJ; Zennadi, R
Published in: Blood Adv
September 10, 2019

Sickle red blood cells (SSRBCs) are adherent to the endothelium, activate leukocyte adhesion, and are deficient in bioactive nitric oxide (NO) adducts such as S-nitrosothiols (SNOs), with reduced ability to induce vasodilation in response to hypoxia. All these pathophysiologic characteristics promote vascular occlusion, the hallmark of sickle cell disease (SCD). Loading hypoxic SSRBCs in vitro with NO followed by reoxygenation significantly decreased epinephrine-activated SSRBC adhesion to the endothelium, the ability of activated SSRBCs to mediate leukocyte adhesion in vitro, and vessel obstruction in vivo. Because transfusion is frequently used in SCD, we also determined the effects of banked (SNO-depleted) red blood cells (RBCs) on vaso-occlusion in vivo. Fresh or 14-day-old normal RBCs (AARBCs) reduced epinephrine-activated SSRBC adhesion to the vascular endothelium and prevented vaso-occlusion. In contrast, AARBCs stored for 30 days failed to decrease activated SSRBC adhesivity or vaso-occlusion, unless these RBCs were loaded with NO. Furthermore, NO loading of SSRBCs increased S-nitrosohemoglobin and modulated epinephrine's effect by upregulating phosphorylation of membrane proteins, including pyruvate kinase, E3 ubiquitin ligase, and the cytoskeletal protein 4.1. Thus, abnormal SSRBC NO/SNO content both contributes to the vaso-occlusive pathophysiology of SCD, potentially by affecting at least protein phosphorylation, and is potentially amenable to correction by (S)NO repletion or by RBC transfusion.

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Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

September 10, 2019

Volume

3

Issue

17

Start / End Page

2586 / 2597

Location

United States

Related Subject Headings

  • Vascular Diseases
  • Phosphorylation
  • Oxygen
  • Nitric Oxide
  • Membrane Proteins
  • Humans
  • Hemoglobins
  • Erythrocytes
  • Erythrocyte Transfusion
  • Endothelium, Vascular
 

Citation

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McMahon, T. J., Shan, S., Riccio, D. A., Batchvarova, M., Zhu, H., Telen, M. J., & Zennadi, R. (2019). Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo. Blood Adv, 3(17), 2586–2597. https://doi.org/10.1182/bloodadvances.2019031633
McMahon, Timothy J., Siqing Shan, Daniel A. Riccio, Milena Batchvarova, Hongmei Zhu, Marilyn J. Telen, and Rahima Zennadi. “Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.Blood Adv 3, no. 17 (September 10, 2019): 2586–97. https://doi.org/10.1182/bloodadvances.2019031633.
McMahon TJ, Shan S, Riccio DA, Batchvarova M, Zhu H, Telen MJ, et al. Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo. Blood Adv. 2019 Sep 10;3(17):2586–97.
McMahon, Timothy J., et al. “Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.Blood Adv, vol. 3, no. 17, Sept. 2019, pp. 2586–97. Pubmed, doi:10.1182/bloodadvances.2019031633.
McMahon TJ, Shan S, Riccio DA, Batchvarova M, Zhu H, Telen MJ, Zennadi R. Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo. Blood Adv. 2019 Sep 10;3(17):2586–2597.

Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

September 10, 2019

Volume

3

Issue

17

Start / End Page

2586 / 2597

Location

United States

Related Subject Headings

  • Vascular Diseases
  • Phosphorylation
  • Oxygen
  • Nitric Oxide
  • Membrane Proteins
  • Humans
  • Hemoglobins
  • Erythrocytes
  • Erythrocyte Transfusion
  • Endothelium, Vascular