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Type: Artigo de periódico
Title: Therapy With Hydroxyurea Is Associated With Reduced Adhesion Molecule Gene And Protein Expression In Sickle Red Cells With A Concomitant Reduction In Adhesive Properties.
Author: Gambero, Sheley
Canalli, Andreia A
Traina, Fabiola
Albuquerque, Dulcinéia M
Saad, Sara T O
Costa, Fernando F
Conran, Nicola
Abstract: Propagation of the vaso-occlusive process in sickle cell anaemia (SCA) is a complex process involving the adhesion of steady-state SCA patients red cells and reticulocytes to the vascular endothelium. The effect of hydroxyurea therapy (HUT) on the adhesive properties of sickle cells and the expression of adhesion molecule genes by erythroid cells of SCA individuals is not yet fully understood. The expressions of the CD36 gene and the VLA-4-integrin subunit genes, CD49d (alpha-subunit) and CD29 (beta-subunit), were compared in the reticulocytes of steady-state SCA patients and patients on HUT using real-time PCR. Basal adhesion of red cells from these subjects was also compared using static adhesion assays, as was surface protein expression, using flow cytometry. Basal sickle red cell adhesion to fibronectin was significantly greater than that of normal cells (P < 0.01); in contrast, HUT was associated with significantly lower levels (P < 0.01) of red cell adhesion that were similar to those of control cells; this decrease could not be justified solely by altered reticulocyte numbers in this population. Accordingly, flow cytometry demonstrated that reticulocytes from patients on HUT had significantly lower CD36 and CD49d surface expressions (P < 0.01) and, importantly, significantly lower expressions of the CD36, CD49d and CD29 genes (P < 0.05) than reticulocytes of SCA patients not on HUT. Taken together, data support the hypothesis that HUT reduces the adhesive properties of sickle cells and that this decrease appears to be mediated, at least in part, by a decrease in the gene and, consequently, surface protein expression of adhesion molecules such as VLA-4 and CD36.
Subject: Adult
Anemia, Sickle Cell
Antigens, Cd29
Antigens, Cd36
Cell Adhesion
Cell Adhesion Molecules
Drug Evaluation
Gene Expression Profiling
Gene Expression Regulation
Integrin Alpha4
Integrin Alpha4beta1
Lutheran Blood-group System
Middle Aged
Neoplasm Proteins
Rna, Messenger
Citation: European Journal Of Haematology. v. 78, n. 2, p. 144-51, 2007-Feb.
Rights: fechado
Identifier DOI: 10.1111/j.1600-0609.2006.00788.x
Date Issue: 2007
Appears in Collections:Unicamp - Artigos e Outros Documentos

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