| Theoretical Aspects of Reactive Oxygen/Nitrogen Species Homeostasis inside Macrophages during Phagocytosis Monitored at Nanoelectrodes Alexander Oleinick1; Xin-wei Zhang2; Irina Svir3; Christian Amatore4; Wei-hua Huang5; 1CNRS-ENS-SU UMR 8640 PASTEUR, CNRS, Paris, France; 2KEY LABORATORY OF ANALYTICAL CHEMISTRY FOR BIOLOGY AND MEDICINE, COLLEGE OF CHEMISTRY AND MOLECULAR SCIENCES, Wuhan, China; 3ECOLE NORMALE SUPERIEURE, DEPARTMENT CHEMISTRY, PARIS, France; 4CNRS & PSL, FRENCH ACAD. OF SCI. AND XIAMEN UNIVERSITY, Paris, France; 5WUHAN UNIVERSITY, Wuhan, China; PAPER: 322/Oxidative/Regular (Oral) SCHEDULED: 16:20/Thu. 24 Oct. 2019/Zeus (55/Mezz. F) ABSTRACT: Traffic of the lipid-enclosed compartments (vesicles, endosomes, phagosomes etc.) within the cell is extremely important for sustaining cell life and allowing the cell to perform its function. These lipid bilayer bound organelles deliver their cargo through bilayer fusion with the other organelles or with the plasma membrane. In the case when the release of the cargo molecule is controlled only by diffusion, we have shown earlier for the case of vesicular exocytosis that emptying of such organelles occurs exponentially and the rate of the exponential decay is controlled by the size of the fusion pore [1]. The generality of the assumptions made for model derivation, as well as for laws underlying this model, suggest that the assumptions can be applied to a vast variety of cases. This can be done independently if organelles fuse with another part like the cellular membrane or electrode (like in vesicle impact electrochemical cytometry), etc. Moreover, being able to describe mass transport of the cargo molecules inside or out of the organelle allow one to characterize various physicochemical processes occurring within the organelle [2]. In particular, relevantly adapted models were applied to the case of the detection with the platinized carbon nanoelectrode of the reactive oxygen/nitrogen species (ROS/RNS) produced by macrophages inside their phagolysosomes (more on the experiment will be presented in Prof. Wei-Hua Huang's talk) [3]. Modelling the oxidation and mass transport of the ROS/RNS towards the nanoelectrode and comparison with experimental data evidenced <u>for the first time</u> that the consumption of ROS/RNS by their oxidation at the nanoelectrode surface stimulates the production of significant ROS/RNS amounts inside phagolysosomes, i.e., proved the very existence of a ROS/RNS homeostasis during phagocytosis. The homeostatic production rates of ROS/RNS inside individual phagolysosomes were quantified by employing the developed theory [3]. These results allowed measuring the long-time postulated ROS/RNS homeostasis within the phagolysosome, its kinetics and its efficiency. ROS/RNS concentrations may then be maintained at sufficiently high levels to sustain proper pathogen digestion rates without endangering the macrophage internal structures [3]. References: 1. A. Oleinick, I. Svir, C. Amatore. Proc. R. Soc. A, 473, 2017, 20160684.<br />2. A. Oleinick, I. Svir, W.-H. Huang, C. Amatore, in preparation.<br />3. X.-W. Zhang, A. Oleinick, H. Jiang, Q.-L. Liao, Q.-F. Qiu, I. Svir, Y.-L. Liu, C. Amatore, W.-H. Huang. Angew. Chem. Ind. Ed., 58, 2019, 7753-7756. |
