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Sickle erythrocyte adherence to endothelium at low shear: Role of shear stress in propagation of vaso‐occlusion
Author(s) -
Montes Richard A.O.,
Eckman James R.,
Hsu Lewis L.,
Wick Timothy M.
Publication year - 2002
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.10145
Subject(s) - endothelium , shear stress , microcirculation , cell adhesion , biophysics , sickle cell anemia , cell adhesion molecule , receptor , endothelial activation , medicine , immunology , adhesion , hemorheology , microbiology and biotechnology , cell , chemistry , biology , biochemistry , materials science , disease , organic chemistry , composite material
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‐α 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. Am. J. Hematol. 70:216–227, 2002. © 2002 Wiley‐Liss, Inc.