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Inflammatory mediators promote strong sickle cell adherence to endothelium under venular flow conditions
Author(s) -
Walmet Paula S.,
Eckman James R.,
Wick Timothy M.
Publication year - 2003
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.10360
Subject(s) - endothelium , sickle cell anemia , venule , medicine , e selectin , endothelial activation , vcam 1 , immunology , endocrinology , cell adhesion , chemistry , cell , cell adhesion molecule , biochemistry , icam 1 , disease
Adherence of sickle erythrocytes to endothelium in venules is thought to initiate or propagate vaso‐occlusive episodes. Because of blood shear forces with normal microvascular flow, adherence in post‐capillary venules requires binding via high‐affinity receptor‐mediated pathways. Microvascular flow in sickle patients is episodic, even in asymptomatic patients, so adherence may also occur at low shear not requiring high‐affinity binding. Sickle cell binding to endothelium was quantified under flow or static incubation with unusually large vWF, thrombospondin, α 4 β 1 /VCAM‐1 or α 4 β 1 /fibronectin (FN). Adherence under flow at 0.5 dyne/cm 2 shear stress leads to the greatest number of adherent sickle cells. Adherence under flow at 1.0 dyne/cm 2 leads to the strongest adherence. Static incubation conditions promote weak adherence of low numbers of sickle cells to endothelium. Following attachment at 1.0 dyne/cm 2 , adherence strength was 2.5 ± 0.1 or 2.6 ± 0.2 dynes/cm 2 for α 4 β 1 /VCAM‐1 or α 4 β 1 /FN pathways, a level 50% greater than adherence strength mediated by thrombospondin or ULvWF (1.7 ± 0.08 or 1.6 ± 0.07 dynes/cm 2 , respectively). Sickle cell adhesion promoted by simultaneous activation of α 4 β 1 /VCAM‐1 and α 4 β 1 /FN pathways is the strongest at 6.2 ± 0.2 dynes/cm 2 and adherent red cells resist detachment shear stresses up to 10 dynes/cm 2 . These data demonstrate that sickle cell adhesion to endothelium is regulated both by receptor/ligand affinity and flow conditions. Thus, both microvascular flow conditions and receptor–ligand interactions may regulate sickle cell adherence in vivo. Am. J. Hematol. 73:215–224, 2003. © 2003 Wiley‐Liss, Inc.