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Accelerated reactivity of blood granulocytes in patients with atopic bronchial asthma out of exacerbation
Authors:Irina V Tikhonova  Ninel I Kosyakova  Andrey A Grinevich  Alexander D Nadeev  Nikolai K Chemeris  Valentina G Safronova
Institution:1. Institute of Cell Biophysics, Russian Academy of Sciences, Institutskaya st., 3, Pushchino, Moscow region, 142290, Russia;2. Hospital of Pushchino Scientific Center, Russian Academy of Sciences, Institutskaya st., 1, Pushchino, Moscow region, 142290, Russia;3. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya st., 3, Pushchino, Moscow region, 142290, Russia;4. ISechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, pr. Torez, 44, Saint Petersburg, 194223, Russia
Abstract:Reactive oxygen species (ROS) are important in bronchial asthma (BA) pathogenesis owing to accumulation of activated granulocytes in the lungs. But the ROS-producing activity of the cells is insufficiently understood in the blood of BA patients. This study analyzes the kinetics of phagocyte respiratory burst in the blood to improve the methods of BA patients monitoring. Patients with atopic BA out of exacerbation (n = 60) and healthy controls (n = 43) were recruited. The time-course of respiratory response to opsonized zymosan (OZ) was recorded in the whole blood using luminol-dependent chemiluminescence (CL), and its activation kinetics (lag-time, rate, amplitude, ROS production) was calculated. The discriminative power of ROS generation kinetics was defined by Receiver Operating Characteristic (ROC) curve analysis. Standard physiological respiratory parameters of patients did not differ from the controls. More rapid response to OZ was recorded in BA patient samples versus the controls. The primed state of phagocytes in the blood of BA patients was corroborated by significant weakening formyl peptide priming effect. The adhesion of granulocytes to cultured human endothelial cells was two-fold higher in BA patients versus controls. ROC curve analysis exhibited good discriminative effectiveness of the CL kinetics to compare BA individuals with the controls. The highest power (86% sensitivity and 90% specificity) was achieved at a linear combination of the parameters. We assume that the assessment of phagocyte reactivity based on the analysis of the response kinetic profile is a good test for monitoring of the state in BA patients.
Keywords:a  u  Arbitrary units  AUC  area under the curve  BA  bronchial asthma  CL  chemiluminescence  CI  confidence interval  CR3  CR4  complement receptors 3 and 4  half maximal effective concentration  FVC  forced vital capacity  fMLF  peptide N-formyl-Met-Leu-Phe  FPR  formyl peptide receptor  GINA  Global Initiative for Asthma  HUVEC  human umbilical vein endothelial cells  ICAM-1  intercellular adhesion molecule 1  IgE  immunoglobulin E  LFA-1  lymphocyte function-associated antigen 1  OZ  opsonized zymosan  PEF  peak expiratory flow  PMA  phorbol 12-myristate 13-acetate  ROC  receiver operating characteristic  ROS  reactive oxygen species  TNF-α  necrosis factor-α  WKYMVM  Phagocyte  Respiratory burst  Kinetics  Receiver operating characteristic  Priming  Adhesion  Allergic bronchial asthma
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