Effect of isopropyl methylphosphonofluoridate (IMPF) poisoning on selected immunological parameters of angiogenesis
Robert Zdanowski 1, Małgorzata Krzyżowska 1, Sławomir Lewicki 2, Piotr Rutkowski 1, Monika Leśniak 3, Marek Saracyn 4, Marcin Niemcewicz 5, Aleksander Michalski 5, Marek Kowalczyk 6 1 - Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Warsaw, Poland 2 - Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Warsaw, Poland 3 - Department of Regenerative Medicine, Military Institute of Hygiene and Epidemiology, Warsaw, Poland 4 - Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Health Services, Warsaw, Poland 5 - Biological Threat Identification and Countermeasure Centre, Military Institute of Hygiene and Epidemiology, Puławy, Poland 6 - Department of Pharmacology and Toxicology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland; Jozef Piłsudski University of Physical Education, Warsaw, Poland Ann Agric Environ Med 2014; 21 (4): ICID: 1129925 Article type: Original article
introduction and objective. Acetylcholinesterase (AChE) and cholinergic receptors play an important role in the immune system, including lymphocyte-induced angiogenesis. However, their exact role is not fully understood. The presented work tests the influence of isopropyl methylphosphonofluoridate (IMPF), an irreversible inhibitor of AChE, on selected immune parameters associated with angiogenesis in mice. The levels of VEGF, bFGF, TNF-α, and IFN-γ production were measured, together with the ability of lymphoid spleen cells to induce local GvH reaction after a single dose of IMPF.
materials and method. Experiments were performed in male BALB/c mice. Acetylcholinesterase activity in erythrocytes was determined by the Ellman`s procedure. Levels of cytokines were measured in serum using standard commercial ELISA kits. Influence of IMPF intoxication upon angiogenesis was examined by the LIA test, according to the Sidky and Auerbach procedure.
results. The results showed a 6- and 8-fold increase in VEGF at days 1 and 7 of the experiment, respectively, as well as a decrease (at days 14 and 21 after administration), followed by a significant increase (day 1) in bFGF levels. A statistically significant decrease in the concentration of IFN-γ was observed throughout all experiments. The maximum decrease in the level of TNF-α was found at days 1 and 7 after administration of IMPF. Additionally, a significant decrease was found in the ability to form new blood vessels following IMPF administration.
conclusions. This study revealed that IMPF has a significant effect on the regulation of lymphocyte-induced angiogenesis, which is related with the modulation of angiogenic and pro-inflammatory cytokines secretion. The observed differences suggest a possible derangement of certain elements of the neuronal and/or non-neuronal cholinergic system.
DOI: 10.5604/12321966.1129925 PMID 25528912 - click here to show this article in PubMed