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Type: Artigo de periódico
Title: Increased Adhesive Properties Of Neutrophils In Sickle Cell Disease May Be Reversed By Pharmacological Nitric Oxide Donation.
Author: Canalli, Andreia A
Franco-Penteado, Carla F
Saad, Sara T O
Conran, Nicola
Costa, Fernando F
Abstract: Increased leukocyte adhesion to vascular endothelium contributes to vaso-occlusion in sickle cell disease. Since nitric oxide bioavailability is decreased in sickle cell disease and nitric oxide may inhibit leukocyte adhesion, we investigated whether stimulation of NO-signaling pathways can reduce the adhesive properties of neutrophils from sickle cell disease individuals (sickle cell diseaseneu). sickle cell diseaseneu presented greater adhesion in vitro to both fibronectin and ICAM-1 than control neutrophils. Co-incubation of sickle cell diseaseneu with the nitric oxide-donor agents, sodium nitroprusside and dietheylamine NONOate (DEANO), and the guanylate cyclase stimulator, BAY41-2272, all significantly reduced the increased adhesion to fibronectin/ICAM-1. Oxadiazolo[4,3-a]quinoxalin-1-one, a guanylate cyclase inhibitor, reversed sodium nitroprusside/DEANO-diminished adhesion to fibronectin, implicating cGMP-dependent signaling in this mechanism. Interestingly, intracellular cGMP was significantly higher in neutrophils from sickle cell disease individuals on hydroxyurea (sickle cell diseaseHUneu). Accordingly, sickle cell diseaseHUneu adhesion to fibronectin/ICAM-1 was significantly lower than that of sickle cell diseaseneu. Agents that stimulate the nitric oxide/cGMP-dependent pathway may have beneficial effects on leukocyte function if used in these subjects.
Subject: Adult
Anemia, Sickle Cell
Antigens, Cd11a
Antigens, Cd11b
Cell Adhesion
Cyclic Gmp
Endothelial Cells
Integrin Alpha4
Intercellular Adhesion Molecule-1
Middle Aged
Nitric Oxide
Nitric Oxide Donors
Sickle Cell Trait
Citation: Haematologica. v. 93, n. 4, p. 605-9, 2008-Apr.
Rights: aberto
Identifier DOI: 10.3324/haematol.12119
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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