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Sickle cell adhesion depends on hemodynamics and endothelial activation.
J Lab Clin Med. 2004 Nov; 144(5):260-7; discussion 227-8.JL

Abstract

Venular microvascular circulation in patients with sickle cell anemia exhibits reduced and episodic blood flow. Sickle erythrocyte adhesion to postcapillary venule endothelium is postulated to initiate and propagate episodes of vasoocclusive pain. Hemodynamics likely mediate the adherence of sickle cells to endothelium, controlling delivery of potentially adherent erythrocytes and removal of loosely adherent erythrocytes on the endothelium. This study found a high dependence on shear stress of sickle erythrocyte adhesion to vascular cell adhesion molecule-1 (VCAM-1) on endothelium stimulated by tumor necrosis factor-alpha (TNF-alpha). Shear stress varied from 1.0 dyne/cm 2 (microvascular venular flow), in which VCAM-1 ligand interactions induced by TNF-alpha primarily controlled adherence, to 0.1 dyne/cm 2 (low flow), in which stimulation had little effect on adherence. At shear stresses analogous to in vivo velocities from laser Doppler ultrasound studies (0.8 and 0.6 dyne/cm 2), TNF-alpha promoted 1.9- and 2.7-fold increases in adhesion compared with unstimulated (baseline) adherence. These findings suggest a dynamic vasoocclusive process that depends on both receptor expression and shear stress. These results indicate that, in the microvasculature, slightly reduced inflow rate, increased receptor expression, or both may result in large increases in sickle erythrocyte adhesion.

Authors+Show Affiliations

Department of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15570244

Citation

Wagner, Matthew C., et al. "Sickle Cell Adhesion Depends On Hemodynamics and Endothelial Activation." The Journal of Laboratory and Clinical Medicine, vol. 144, no. 5, 2004, pp. 260-7; discussion 227-8.
Wagner MC, Eckman JR, Wick TM. Sickle cell adhesion depends on hemodynamics and endothelial activation. J Lab Clin Med. 2004;144(5):260-7; discussion 227-8.
Wagner, M. C., Eckman, J. R., & Wick, T. M. (2004). Sickle cell adhesion depends on hemodynamics and endothelial activation. The Journal of Laboratory and Clinical Medicine, 144(5), 260-7; discussion 227-8.
Wagner MC, Eckman JR, Wick TM. Sickle Cell Adhesion Depends On Hemodynamics and Endothelial Activation. J Lab Clin Med. 2004;144(5):260-7; discussion 227-8. PubMed PMID: 15570244.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sickle cell adhesion depends on hemodynamics and endothelial activation. AU - Wagner,Matthew C, AU - Eckman,James R, AU - Wick,Timothy M, PY - 2004/12/1/pubmed PY - 2004/12/24/medline PY - 2004/12/1/entrez SP - 260-7; discussion 227-8 JF - The Journal of laboratory and clinical medicine JO - J Lab Clin Med VL - 144 IS - 5 N2 - Venular microvascular circulation in patients with sickle cell anemia exhibits reduced and episodic blood flow. Sickle erythrocyte adhesion to postcapillary venule endothelium is postulated to initiate and propagate episodes of vasoocclusive pain. Hemodynamics likely mediate the adherence of sickle cells to endothelium, controlling delivery of potentially adherent erythrocytes and removal of loosely adherent erythrocytes on the endothelium. This study found a high dependence on shear stress of sickle erythrocyte adhesion to vascular cell adhesion molecule-1 (VCAM-1) on endothelium stimulated by tumor necrosis factor-alpha (TNF-alpha). Shear stress varied from 1.0 dyne/cm 2 (microvascular venular flow), in which VCAM-1 ligand interactions induced by TNF-alpha primarily controlled adherence, to 0.1 dyne/cm 2 (low flow), in which stimulation had little effect on adherence. At shear stresses analogous to in vivo velocities from laser Doppler ultrasound studies (0.8 and 0.6 dyne/cm 2), TNF-alpha promoted 1.9- and 2.7-fold increases in adhesion compared with unstimulated (baseline) adherence. These findings suggest a dynamic vasoocclusive process that depends on both receptor expression and shear stress. These results indicate that, in the microvasculature, slightly reduced inflow rate, increased receptor expression, or both may result in large increases in sickle erythrocyte adhesion. SN - 0022-2143 UR - https://www.unboundmedicine.com/medline/citation/15570244/Sickle_cell_adhesion_depends_on_hemodynamics_and_endothelial_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022214304002203 DB - PRIME DP - Unbound Medicine ER -