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Double-stranded RNA induces sickle erythrocyte adherence to endothelium: a potential role for viral infection in vaso-occlusive pain episodes in sickle cell anemia.
Blood. 1995 May 15; 85(10):2945-50.Blood

Abstract

Vaso-occlusive pain episodes in sickle cell anemia are hypothesized to be precipitated by adherence of sickle erythrocytes to vascular endothelium in the microcirculation. Febrile episodes, thought to be viral in etiology, are frequently associated with vaso-occlusion; however, a direct link between viral infection and vascular occlusion has not yet been established. Many pathogenic viruses contain double-stranded RNA or replicate through double-stranded RNA intermediates. Double-stranded RNA has been shown to induce vascular cell adhesion molecule-1 (VCAM-1) protein expression on endothelial cells. Recently, a new adhesion pathway has been described between VCAM-1 expressed on cytokine stimulated endothelium and the alpha 4 beta 1 integrin complex expressed on sickle reticulocytes. Based on these observations, the hypothesis was developed that viral infection, through double-stranded RNA intermediates, increases endothelial VCAM-1 expression leading to sickle erythrocyte adhesion to endothelium via an alpha 4 beta 1-VCAM-1--dependent mechanism. In support of this hypothesis, endothelial cells exposed to the synthetic double-stranded RNA poly(I:C) or the RNA virus parainfluenza 1 (Sendai virus) express increased levels of VCAM-1 and support increased sickle erythrocyte adherence under continuous flow at 1.0 dyne/cm2 shear stress as compared with unstimulated endothelium. Blocking antibodies directed against either VCAM-1 on the endothelium or alpha 4 beta 1 on sickle erythrocytes inhibit nearly all of the increased sickle cell adherence caused by poly(I:C) or Sendai virus. These results support the hypothesis that viruses, through double-stranded RNA elements, can induce sickle erythrocyte adherence to endothelium through alpha 4 beta 1-VCAM-1--mediated adhesion and provide a potential link between viral infection and microvascular occlusion precipitating sickle cell pain episodes.

Authors+Show Affiliations

School of Chemical Engineering, Georgia Institute of Technology, Atlanta 30332-0100, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7537985

Citation

Smolinski, P A., et al. "Double-stranded RNA Induces Sickle Erythrocyte Adherence to Endothelium: a Potential Role for Viral Infection in Vaso-occlusive Pain Episodes in Sickle Cell Anemia." Blood, vol. 85, no. 10, 1995, pp. 2945-50.
Smolinski PA, Offermann MK, Eckman JR, et al. Double-stranded RNA induces sickle erythrocyte adherence to endothelium: a potential role for viral infection in vaso-occlusive pain episodes in sickle cell anemia. Blood. 1995;85(10):2945-50.
Smolinski, P. A., Offermann, M. K., Eckman, J. R., & Wick, T. M. (1995). Double-stranded RNA induces sickle erythrocyte adherence to endothelium: a potential role for viral infection in vaso-occlusive pain episodes in sickle cell anemia. Blood, 85(10), 2945-50.
Smolinski PA, et al. Double-stranded RNA Induces Sickle Erythrocyte Adherence to Endothelium: a Potential Role for Viral Infection in Vaso-occlusive Pain Episodes in Sickle Cell Anemia. Blood. 1995 May 15;85(10):2945-50. PubMed PMID: 7537985.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Double-stranded RNA induces sickle erythrocyte adherence to endothelium: a potential role for viral infection in vaso-occlusive pain episodes in sickle cell anemia. AU - Smolinski,P A, AU - Offermann,M K, AU - Eckman,J R, AU - Wick,T M, PY - 1995/5/15/pubmed PY - 1995/5/15/medline PY - 1995/5/15/entrez SP - 2945 EP - 50 JF - Blood JO - Blood VL - 85 IS - 10 N2 - Vaso-occlusive pain episodes in sickle cell anemia are hypothesized to be precipitated by adherence of sickle erythrocytes to vascular endothelium in the microcirculation. Febrile episodes, thought to be viral in etiology, are frequently associated with vaso-occlusion; however, a direct link between viral infection and vascular occlusion has not yet been established. Many pathogenic viruses contain double-stranded RNA or replicate through double-stranded RNA intermediates. Double-stranded RNA has been shown to induce vascular cell adhesion molecule-1 (VCAM-1) protein expression on endothelial cells. Recently, a new adhesion pathway has been described between VCAM-1 expressed on cytokine stimulated endothelium and the alpha 4 beta 1 integrin complex expressed on sickle reticulocytes. Based on these observations, the hypothesis was developed that viral infection, through double-stranded RNA intermediates, increases endothelial VCAM-1 expression leading to sickle erythrocyte adhesion to endothelium via an alpha 4 beta 1-VCAM-1--dependent mechanism. In support of this hypothesis, endothelial cells exposed to the synthetic double-stranded RNA poly(I:C) or the RNA virus parainfluenza 1 (Sendai virus) express increased levels of VCAM-1 and support increased sickle erythrocyte adherence under continuous flow at 1.0 dyne/cm2 shear stress as compared with unstimulated endothelium. Blocking antibodies directed against either VCAM-1 on the endothelium or alpha 4 beta 1 on sickle erythrocytes inhibit nearly all of the increased sickle cell adherence caused by poly(I:C) or Sendai virus. These results support the hypothesis that viruses, through double-stranded RNA elements, can induce sickle erythrocyte adherence to endothelium through alpha 4 beta 1-VCAM-1--mediated adhesion and provide a potential link between viral infection and microvascular occlusion precipitating sickle cell pain episodes. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/7537985/Double_stranded_RNA_induces_sickle_erythrocyte_adherence_to_endothelium:_a_potential_role_for_viral_infection_in_vaso_occlusive_pain_episodes_in_sickle_cell_anemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)76470-0 DB - PRIME DP - Unbound Medicine ER -