Recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes. Methods: We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/744568 de novo/remodelling PAF biosynthesis and PAF PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/21715270 degradation, respectively. Results: Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentrationdepended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, while when combined they synergistically inhibited PAF. Higher concentrations of all antibiotics tested were needed in order to inhibit PAF induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of WRPs. Concentrations of these drugs similar to their IC50 values against PAF activity in WRPs, inhibited also in vitro PAFCPT and Lyso-PAF-AT activities of rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit plasma-PAF-AH activity. Conclusions: These newly found properties of antibiotics used in sepsis suggest that apart from their general actions, these drugs may present additional beneficial anti-inflammatory and anti-coagulant effects against the onset and establishment of sepsis by inhibiting the PAF/PAF-receptor and/or the thrombin/protease-activatedreceptor-1 systems, and/or by reducing PAF-levels through both PAF-biosynthesis inhibition and PAF-catabolism induction. These promising in vitro results need to be further studied and confirmed by in vivo tests, in order to optimize the efficacy of antibiotic treatment in sepsis. Keywords: Antibiotics, Lyso-PAF-AT, PAF, PAF-CPT, PAF-inhibitors, plasma-PAF-AH, Sepsis* Correspondence: atsoupras@yahoo.gr 1 Faculty of Chemistry, National Kapodistrian University of Athens, Panepistimioupolis of Zografou, Athens, 15771, Greece Full list of author information is available at the end of the article?2011 Tsoupras et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Tsoupras et al. Journal of Inflammation 2011, 8:17 http://www.journal-inflammation.com/content/8/1/Page 2 ofBackground Platelet Activating Factor (PAF) is a phospholipid signalling molecule of inflammation and a significant mediator N-BOC-3-Fluoro-D-phenylalanine of the immune system [1,2]. PAF transmits outside-in signals to intracellular transduction systems in a variety of cell types, including key cells of the innate immune and haemostatic systems: neutrophils, monocytes, and platelets [2]. Binding of PAF on specific membrane receptors 1-Methoxy-N-methylpropan-2-amine hydrochloride coupled with G-proteins (PAF-receptor, PAFR) induces several intracellular signaling pathways that leads to auto/endo/para/juxta-crine cellular activation [3]. PAF can be synthesize.
A Ciência & Ensino é uma publicação semestral destinada a professores de ciências do ensino fundamental e médio e seus formadores.
Recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the
por Carin Hanton (2024-03-19)
Recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes. Methods: We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/744568 de novo/remodelling PAF biosynthesis and PAF PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/21715270 degradation, respectively. Results: Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentrationdepended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, while when combined they synergistically inhibited PAF. Higher concentrations of all antibiotics tested were needed in order to inhibit PAF induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of WRPs. Concentrations of these drugs similar to their IC50 values against PAF activity in WRPs, inhibited also in vitro PAFCPT and Lyso-PAF-AT activities of rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit plasma-PAF-AH activity. Conclusions: These newly found properties of antibiotics used in sepsis suggest that apart from their general actions, these drugs may present additional beneficial anti-inflammatory and anti-coagulant effects against the onset and establishment of sepsis by inhibiting the PAF/PAF-receptor and/or the thrombin/protease-activatedreceptor-1 systems, and/or by reducing PAF-levels through both PAF-biosynthesis inhibition and PAF-catabolism induction. These promising in vitro results need to be further studied and confirmed by in vivo tests, in order to optimize the efficacy of antibiotic treatment in sepsis. Keywords: Antibiotics, Lyso-PAF-AT, PAF, PAF-CPT, PAF-inhibitors, plasma-PAF-AH, Sepsis* Correspondence: atsoupras@yahoo.gr 1 Faculty of Chemistry, National Kapodistrian University of Athens, Panepistimioupolis of Zografou, Athens, 15771, Greece Full list of author information is available at the end of the article?2011 Tsoupras et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Tsoupras et al. Journal of Inflammation 2011, 8:17 http://www.journal-inflammation.com/content/8/1/Page 2 ofBackground Platelet Activating Factor (PAF) is a phospholipid signalling molecule of inflammation and a significant mediator N-BOC-3-Fluoro-D-phenylalanine of the immune system [1,2]. PAF transmits outside-in signals to intracellular transduction systems in a variety of cell types, including key cells of the innate immune and haemostatic systems: neutrophils, monocytes, and platelets [2]. Binding of PAF on specific membrane receptors 1-Methoxy-N-methylpropan-2-amine hydrochloride coupled with G-proteins (PAF-receptor, PAFR) induces several intracellular signaling pathways that leads to auto/endo/para/juxta-crine cellular activation [3]. PAF can be synthesize.