caa a22 4500 44588519X CHVBK 20180317145557.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s00011-011-0315-8 doi (NATIONALLICENCE)springer-10.1007/s00011-011-0315-8 Inhibition of phosphodiesterase 9A reduces cytokine-stimulated in vitro adhesion of neutrophils from sickle cell anemia individuals [Elektronische Daten] [Lediana Miguel, Camila Almeida, Fabiola Traina, Andreia Canalli, Venina Dominical, Sara Saad, Fernando Costa, Nicola Conran] Objective: Leukocyte adhesion to vessel walls may initiate vaso-occlusion in sickle cell anemia (SCA); however, the extent to which inflammation participates in this mechanism is not understood. This in vitro study investigated whether inflammatory molecules, commonly augmented in SCA, can affect neutrophil adhesive properties and whether cyclic guanosine monophosphate (cGMP)-elevating agents can inhibit such adhesion. Subjects and methods: Effects of Interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α), granulocyte macrophage-colony stimulating factor (GM-CSF) cytokines, BAY 73-6691 [phosphodiesterase (PDE)-9A-inhibitor], and BAY 41-2271 (guanylate-cylase stimulator) on the adhesive properties of neutrophils from healthy control (CON) and steady-state SCA individuals were determined using static-adhesion assays. Results: SCA neutrophils demonstrated increased adhesive properties, compared to CON neutrophils; IL-8, TNF-α and GM-CSF increased CON neutrophil adhesion and further increased SCA neutrophil adhesion to fibronectin (FN). The PDE9A inhibitor, BAY-73-6691, significantly reduced basal CON neutrophil and SCA neutrophil adhesion; this was accompanied by decreased SCA neutrophil surface expressions of the L-selectin and CD11b adhesion molecules. BAY-73-6691 also significantly reduced cytokine-stimulated CON neutrophil and SCA neutrophil adhesion to FN; however, this was not accompanied by alterations in adhesion-molecule presentation. Conclusions: The chronic inflammatory nature of SCA may contribute to leukocyte adhesive functions in SCA. Furthermore, elevation of leukocyte cGMP may be an interesting approach for inhibition of leukocyte adhesion to the vessel wall, even in the presence of inflammatory stimuli. Springer Basel AG, 2011 cGMP nationallicence Cytokine nationallicence Inflammation nationallicence Leukocyte nationallicence Sickle cell anemia nationallicence Vaso-occlusion nationallicence Miguel Lediana Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut Almeida Camila Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut Traina Fabiola Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut Canalli Andreia Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut Dominical Venina Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut Saad Sara Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut Costa Fernando Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut Conran Nicola Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut Inflammation Research SP Birkhäuser Verlag Basel 60/7(2011-07-01), 633-642 1023-3830 60:7<633 2011 60 11 https://doi.org/10.1007/s00011-011-0315-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0315-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Miguel Lediana Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut NATIONALLICENCE 700 1- Almeida Camila Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut NATIONALLICENCE 700 1- Traina Fabiola Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut NATIONALLICENCE 700 1- Canalli Andreia Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut NATIONALLICENCE 700 1- Dominical Venina Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut NATIONALLICENCE 700 1- Saad Sara Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut NATIONALLICENCE 700 1- Costa Fernando Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut NATIONALLICENCE 700 1- Conran Nicola Hematology and Hemotherapy Center - Instituto Nacional de Ciência e Tecnologia do Sangue (INCTS), University of Campinas - UNICAMP, 13083-970, Campinas, SP, Brazil aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/7(2011-07-01), 633-642 1023-3830 60:7<633 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer