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Hydroxyurea attenuates activated neutrophil-mediated sickle erythrocyte membrane phosphatidylserine exposure and adhesion to pulmonary vascular endothelium.
Am J Physiol Heart Circ Physiol 2008; 294(1):H379-85AJ

Abstract

Activated neutrophils increase erythrocyte phosphatidylserine (PS) exposure. PS-exposed sickle red blood cells (SSRBCs) are more adhesive to vascular endothelium than non-PS-exposed cells. An increase in SSRBC fetal hemoglobin (HbF) concentration has been associated with improved rheology and decreased numbers of vasoocclusive episodes. This study examined the effects of HbF, PS-exposed SSRBCs, and chronic hydroxyurea (HU) treatment on activated neutrophil-mediated SSRBC retention/adherence in isolated-perfused rat lungs. Lungs were perfused with erythrocyte suspensions from 1) individuals homozygous for hemoglobin S with 0-7% HbF (SS), 2) with > or =8% HbF (SS + F), and 3) individuals homozygous for hemoglobin S treated with HU therapy for > or =1 yr (SS + HU). Retention of SSRBCs from the SS + HU group was significantly less than that seen in both the SS and SS + F groups. No difference was observed between the SS and SS + F groups. The percentage of HbF and F-cells did not differ between the SS + F and SS + HU groups. At baseline, the proportion of PS-exposed SSRBCs was not different between the SS and SS + HU groups. However, SSRBC treatment with activated neutrophil supernatant caused a twofold increase in PS-exposed SSRBCs in the SS control and no change in the SS + HU group. We conclude that 1) HU attenuates SSRBC retention/adherence in the pulmonary circulation seen in response neutrophil activation, 2) HU stabilizes SSRBC membrane PS, and 3) HU attenuation SSRBC retention/adherence in the pulmonary circulation occurs through a mechanism(s) independent of HbF.

Authors+Show Affiliations

Comprehensive Sickle Cell Center, Department of Medicine, University of South Alabama Medical Center, 2451 Fillingim Street, Mobile, AL 36617, USA. jhaynes@usouthal.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17993595

Citation

Haynes, Johnson, et al. "Hydroxyurea Attenuates Activated Neutrophil-mediated Sickle Erythrocyte Membrane Phosphatidylserine Exposure and Adhesion to Pulmonary Vascular Endothelium." American Journal of Physiology. Heart and Circulatory Physiology, vol. 294, no. 1, 2008, pp. H379-85.
Haynes J, Obiako B, Hester RB, et al. Hydroxyurea attenuates activated neutrophil-mediated sickle erythrocyte membrane phosphatidylserine exposure and adhesion to pulmonary vascular endothelium. Am J Physiol Heart Circ Physiol. 2008;294(1):H379-85.
Haynes, J., Obiako, B., Hester, R. B., Baliga, B. S., & Stevens, T. (2008). Hydroxyurea attenuates activated neutrophil-mediated sickle erythrocyte membrane phosphatidylserine exposure and adhesion to pulmonary vascular endothelium. American Journal of Physiology. Heart and Circulatory Physiology, 294(1), pp. H379-85.
Haynes J, et al. Hydroxyurea Attenuates Activated Neutrophil-mediated Sickle Erythrocyte Membrane Phosphatidylserine Exposure and Adhesion to Pulmonary Vascular Endothelium. Am J Physiol Heart Circ Physiol. 2008;294(1):H379-85. PubMed PMID: 17993595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydroxyurea attenuates activated neutrophil-mediated sickle erythrocyte membrane phosphatidylserine exposure and adhesion to pulmonary vascular endothelium. AU - Haynes,Johnson,Jr AU - Obiako,Boniface, AU - Hester,Raymond B, AU - Baliga,B Surendra, AU - Stevens,Troy, Y1 - 2007/11/09/ PY - 2007/11/13/pubmed PY - 2008/2/29/medline PY - 2007/11/13/entrez SP - H379 EP - 85 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 294 IS - 1 N2 - Activated neutrophils increase erythrocyte phosphatidylserine (PS) exposure. PS-exposed sickle red blood cells (SSRBCs) are more adhesive to vascular endothelium than non-PS-exposed cells. An increase in SSRBC fetal hemoglobin (HbF) concentration has been associated with improved rheology and decreased numbers of vasoocclusive episodes. This study examined the effects of HbF, PS-exposed SSRBCs, and chronic hydroxyurea (HU) treatment on activated neutrophil-mediated SSRBC retention/adherence in isolated-perfused rat lungs. Lungs were perfused with erythrocyte suspensions from 1) individuals homozygous for hemoglobin S with 0-7% HbF (SS), 2) with > or =8% HbF (SS + F), and 3) individuals homozygous for hemoglobin S treated with HU therapy for > or =1 yr (SS + HU). Retention of SSRBCs from the SS + HU group was significantly less than that seen in both the SS and SS + F groups. No difference was observed between the SS and SS + F groups. The percentage of HbF and F-cells did not differ between the SS + F and SS + HU groups. At baseline, the proportion of PS-exposed SSRBCs was not different between the SS and SS + HU groups. However, SSRBC treatment with activated neutrophil supernatant caused a twofold increase in PS-exposed SSRBCs in the SS control and no change in the SS + HU group. We conclude that 1) HU attenuates SSRBC retention/adherence in the pulmonary circulation seen in response neutrophil activation, 2) HU stabilizes SSRBC membrane PS, and 3) HU attenuation SSRBC retention/adherence in the pulmonary circulation occurs through a mechanism(s) independent of HbF. SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/17993595/Hydroxyurea_attenuates_activated_neutrophil_mediated_sickle_erythrocyte_membrane_phosphatidylserine_exposure_and_adhesion_to_pulmonary_vascular_endothelium_ L2 - http://www.physiology.org/doi/full/10.1152/ajpheart.01068.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -