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This Article Full Text Full Text (PDF) All Versions of this Article: 291/4/H1679    most recent 00256.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Haynes, J. Articles by Ofori-Acquah, S. Search for Related Content PubMed PubMed Citation Articles by Haynes, J., Jr. Articles by Ofori-Acquah, S.

Activated neutrophil-mediated sickle red blood cell adhesion to lung vascular endothelium: role of phosphatidylserine-exposed sickle red blood cells

¹University of South Alabama Comprehensive Sickle Cell Center, and Departments of ²Medicine, ³Pharmacology, ⁴Pathology, ⁵Microbiology, and ⁶Cell Biology and Neuroscience, University of South Alabama College of Medicine, Mobile, Alabama

Submitted 13 March 2006 ; accepted in final form 11 May 2006

Activated neutrophils (ANs) increase sickle red blood cell (SRBC) retention/adhesion in the pulmonary circulation. This study investigates the role of neutrophil activation and SRBC retention/adhesion in the pulmonary circulation through a mechanism that involves increasing phosphatidylserine (PS) exposure on the external membrane surface of the SRBCs (PS-exposed). With the use of flow cytometry, double-labeling studies were performed with a calcium-dependent phospholipid-binding protein, annexin V-fluorescein isothiocyanate fluorescence, and the erythroid-specific marker glycophorin A to assess for the percentage of PS-exposed normal and SRBCs at baseline and after coincubation with ANs. Additional studies were performed that assessed retention/adhesion of SRBCs in the isolated rat lung using ⁵¹Cr-labeled SRBC alone, SRBC + AN, SRBC + AN + zileuton, and SRBC + AN + annexin V. Specific activities of lung and perfusate were measured, and the number of retained SRBCs per gram lung was calculated. Flow cytometry demonstrated that ANs increased the percentage of PS-exposed normal and SRBCs. The 5-lipoxygenase inhibitor zileuton attenuated AN-mediated increases in PS-exposed SRBCs and decreased SRBC retention/adherence in the lung on histological sections. Similarly, in the isolated perfused lung and in histological lung sections, retention/adherence of SRBCs cloaked with annexin V was attenuated in the presence of ANs. We conclude that ANs enhance the adhesion of SRBCs to vascular endothelium by increasing red blood cell membrane externalization of PS. Zileuton attenuation of AN-mediated SRBC PS externalization suggests that a 5-lipoxygenase product(s), secreted by the AN, plays a vital role in altering the adhesive properties of PS-exposed SRBCs to vascular endothelium.

zileuton; microvascular occlusion; pulmonary circulation

This article has been cited by other articles:

				J. Haynes Jr., B. Obiako, R. B. Hester, B. S. Baliga, and T. Stevens Hydroxyurea attenuates activated neutrophil-mediated sickle erythrocyte membrane phosphatidylserine exposure and adhesion to pulmonary vascular endothelium Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H379 - H385. [Abstract] [Full Text] [PDF]