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Inflammatory mediators promote strong sickle cell adherence to endothelium under venular flow conditions.
Am J Hematol. 2003 Aug; 73(4):215-24.AJ

Abstract

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, alpha(4)beta(1)/VCAM-1 or alpha(4)beta(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 alpha(4)beta(1)/VCAM-1 or alpha(4)beta(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 alpha(4)beta(1)/VCAM-1 and alpha(4)beta(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.

Authors+Show Affiliations

School of Chemical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332-0100, 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

12879422

Citation

Walmet, Paula S., et al. "Inflammatory Mediators Promote Strong Sickle Cell Adherence to Endothelium Under Venular Flow Conditions." American Journal of Hematology, vol. 73, no. 4, 2003, pp. 215-24.
Walmet PS, Eckman JR, Wick TM. Inflammatory mediators promote strong sickle cell adherence to endothelium under venular flow conditions. Am J Hematol. 2003;73(4):215-24.
Walmet, P. S., Eckman, J. R., & Wick, T. M. (2003). Inflammatory mediators promote strong sickle cell adherence to endothelium under venular flow conditions. American Journal of Hematology, 73(4), 215-24.
Walmet PS, Eckman JR, Wick TM. Inflammatory Mediators Promote Strong Sickle Cell Adherence to Endothelium Under Venular Flow Conditions. Am J Hematol. 2003;73(4):215-24. PubMed PMID: 12879422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammatory mediators promote strong sickle cell adherence to endothelium under venular flow conditions. AU - Walmet,Paula S, AU - Eckman,James R, AU - Wick,Timothy M, PY - 2003/7/25/pubmed PY - 2003/9/17/medline PY - 2003/7/25/entrez SP - 215 EP - 24 JF - American journal of hematology JO - Am J Hematol VL - 73 IS - 4 N2 - 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, alpha(4)beta(1)/VCAM-1 or alpha(4)beta(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 alpha(4)beta(1)/VCAM-1 or alpha(4)beta(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 alpha(4)beta(1)/VCAM-1 and alpha(4)beta(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. SN - 0361-8609 UR - https://www.unboundmedicine.com/medline/citation/12879422/Inflammatory_mediators_promote_strong_sickle_cell_adherence_to_endothelium_under_venular_flow_conditions_ L2 - https://doi.org/10.1002/ajh.10360 DB - PRIME DP - Unbound Medicine ER -