New sickle cell anemia findings from State University of Campinas published
2007 NOV 5 -- Current study results from the report, 'Role for cAMP-protein kinase A signalling in augmented neutrophil adhesion and chemotaxis in sickle cell disease,' have been published. "The significance of the leukocyte in sickle cell disease (SCD) pathophysiology is becoming increasingly recognised; we sought to examine whether the chemotactic properties of neutrophils of SCD individuals may be altered and, further, to better understand the signalling events that mediate altered SCD neutrophil function. Adhesion to immobilised fibronectin (FN) and chemotaxis of control and SCD neutrophils were assessed using in vitro static adhesion assays and 96-well chemotaxis chamber assays," scientists writing in the European Journal of Haematology report. "Adhesion assays confirmed a significantly higher basal adhesion of SCD neutrophils to FN, compared with control neutrophils. Chemotaxis assays established, for the first time, that SCD neutrophils demonstrate greater spontaneous migration and, also, augmented migration in response to IL-8, when compared with control neutrophils. Co-incubation of SCD neutrophils with KT5720 (an inhibitor of PKA) abrogated increased basal SCD neutrophil adhesion, spontaneous chemotaxis and IL-8-stimulated chemotaxis. Stimulation of SCD neutrophils with IL-8 also significantly augmented SCD neutrophil adhesion to FN with a concomitant increase in cAMP levels and this increase in adhesion was abolished by KT5720. Interestingly, the adhesive properties of neutrophils from SCD individuals on hydroxyurea therapy were not significantly altered and results indicate that a reduction in intracellular cAMP may contribute to lower the adhesive properties of these cells. Data indicate that up-regulated cAMP signalling plays a significant role in the altered adhesive and migratory properties in SCD neutrophils," wrote A.A. Canalli and colleagues, State University of Campinas. The researchers concluded: "Such alterations may have important implications for the pathophysiology of the disease and the cAMP-PKA pathway may represent a therapeutic target for the abrogation of altered leukocyte function." Canalli and colleagues published their study in European Journal of Haematology (Role for cAMP-protein kinase A signalling in augmented neutrophil adhesion and chemotaxis in sickle cell disease. European Journal of Haematology, 2007;79(4):330-7). Additional information can be obtained by contacting A.A. Canalli, State University of Campinas-UNICAMP, The Haematology and Haemotherapy Centre, Campinas, SP, Brazil. The publisher of the European Journal of Haematology can be contacted at: Blackwell Munksgaard, 35 Norre Sogade, PO Box 2148, DK-1016 Copenhagen, Denmark. Keywords: Brazil, Campinas, Enzyme Research, Hematology, Kinase, Sickle Cell Anemia, Sickle Cell Disease. This article was prepared by Hematology Week editors from staff and other reports. Copyright 2007, Hematology Week via NewsRx.com.
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