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Sickle erythrocyte adherence to endothelium at low shear: role of shear stress in propagation of vaso-occlusion.
Am J Hematol. 2002 Jul; 70(3):216-27.AJ

Abstract

Under venular flow conditions, sickle cell adherence to endothelium is mediated by cell adhesion molecules and adhesive proteins associated with inflammation, coagulation, and endothelial perturbation. Periodic and reduced blood flow are observed in sickle microcirculation during hematologic steady state, suggesting that blood flow is compromised in sickle microcirculation. We tested the hypothesis that low blood flow enhances adherence by quantifying sickle cell adhesion to endothelium under venular flow (1.0 dyne/cm(2) shear stress) and low flow (0.1 dyne/cm(2) shear stress), with and without addition of adhesion promoting agonists. Under low flow, sickle cell adherence to endothelium increases with contact time in the absence of endothelial activation or adhesive protein addition. In contrast, at venular shear stress, sickle cell adherence only occurs following endothelial activation with TNF-alpha or addition of thrombospondin. Analysis of these data with a mathematical model reveals that at low flow adherence is "transport-controlled," meaning that contact time between sickle cells and endothelium is a more important determinant of adherence than high-affinity receptor-ligand interactions. Low-affinity interactions are sufficient for adhesion at low flow. In contrast, at venular flow (1 dyne/cm(2) shear stress) adherence is "affinity-controlled," meaning that adherence requires induction of specific high-affinity receptor-ligand interactions. These findings demonstrate that in addition to activating factors and adherence proteins, microvascular shear stress is an important determinant of sickle cell adhesion to endothelium. This suggests that in vivo, erythrostasis is an important determinant of adhesion that can act either independently or concurrently with ongoing acute events to induce adhesive interactions and vaso-occlusion.

Authors+Show Affiliations

School of Chemical Engineering, Georgia Institute of Technology, Atlanta, Georgia 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

12111767

Citation

Montes, Richard A O., et al. "Sickle Erythrocyte Adherence to Endothelium at Low Shear: Role of Shear Stress in Propagation of Vaso-occlusion." American Journal of Hematology, vol. 70, no. 3, 2002, pp. 216-27.
Montes RA, Eckman JR, Hsu LL, et al. Sickle erythrocyte adherence to endothelium at low shear: role of shear stress in propagation of vaso-occlusion. Am J Hematol. 2002;70(3):216-27.
Montes, R. A., Eckman, J. R., Hsu, L. L., & Wick, T. M. (2002). Sickle erythrocyte adherence to endothelium at low shear: role of shear stress in propagation of vaso-occlusion. American Journal of Hematology, 70(3), 216-27.
Montes RA, et al. Sickle Erythrocyte Adherence to Endothelium at Low Shear: Role of Shear Stress in Propagation of Vaso-occlusion. Am J Hematol. 2002;70(3):216-27. PubMed PMID: 12111767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sickle erythrocyte adherence to endothelium at low shear: role of shear stress in propagation of vaso-occlusion. AU - Montes,Richard A O, AU - Eckman,James R, AU - Hsu,Lewis L, AU - Wick,Timothy M, PY - 2002/7/12/pubmed PY - 2002/7/27/medline PY - 2002/7/12/entrez SP - 216 EP - 27 JF - American journal of hematology JO - Am J Hematol VL - 70 IS - 3 N2 - Under venular flow conditions, sickle cell adherence to endothelium is mediated by cell adhesion molecules and adhesive proteins associated with inflammation, coagulation, and endothelial perturbation. Periodic and reduced blood flow are observed in sickle microcirculation during hematologic steady state, suggesting that blood flow is compromised in sickle microcirculation. We tested the hypothesis that low blood flow enhances adherence by quantifying sickle cell adhesion to endothelium under venular flow (1.0 dyne/cm(2) shear stress) and low flow (0.1 dyne/cm(2) shear stress), with and without addition of adhesion promoting agonists. Under low flow, sickle cell adherence to endothelium increases with contact time in the absence of endothelial activation or adhesive protein addition. In contrast, at venular shear stress, sickle cell adherence only occurs following endothelial activation with TNF-alpha or addition of thrombospondin. Analysis of these data with a mathematical model reveals that at low flow adherence is "transport-controlled," meaning that contact time between sickle cells and endothelium is a more important determinant of adherence than high-affinity receptor-ligand interactions. Low-affinity interactions are sufficient for adhesion at low flow. In contrast, at venular flow (1 dyne/cm(2) shear stress) adherence is "affinity-controlled," meaning that adherence requires induction of specific high-affinity receptor-ligand interactions. These findings demonstrate that in addition to activating factors and adherence proteins, microvascular shear stress is an important determinant of sickle cell adhesion to endothelium. This suggests that in vivo, erythrostasis is an important determinant of adhesion that can act either independently or concurrently with ongoing acute events to induce adhesive interactions and vaso-occlusion. SN - 0361-8609 UR - https://www.unboundmedicine.com/medline/citation/12111767/Sickle_erythrocyte_adherence_to_endothelium_at_low_shear:_role_of_shear_stress_in_propagation_of_vaso_occlusion_ L2 - https://doi.org/10.1002/ajh.10145 DB - PRIME DP - Unbound Medicine ER -