{"id":499,"date":"2019-01-01T11:04:45","date_gmt":"2019-01-01T11:04:45","guid":{"rendered":"http:\/\/clinicalbiochemistry.net\/?page_id=499"},"modified":"2019-01-19T09:24:08","modified_gmt":"2019-01-19T09:24:08","slug":"acetlycholine-monomeric-c-reactive-protein","status":"publish","type":"page","link":"http:\/\/clinicalbiochemistry.net\/?page_id=499","title":{"rendered":"Acetlycholine & Monomeric C-Reactive Protein"},"content":{"rendered":"\n

Slevin, M., Lemma, R.S., Zeinolabediny, Y., Liu, D., Ferris, G.R., Caprio, V., Phillips, N., Di Napoli, M., Guo, B., Zeng, X., AlBaradie, R., Binsaleh, N.K.,\u00a0McDowell, G<\/strong>. & Fang, W-H. (2018) Acetylcholine inhibits monomeric C-Reactive Protein inducd inflammation, endothelial cell adhesion and platelet aggregation; A potential therapeutic. <\/strong>Frontiers in Immunology 9 article 2124<\/p>\n\n\n\n

Objectives:<\/strong>In this study, we examined the possibility of using targeted antibodies and the potential of small molecular therapeutics (acetylcholine, nicotine and tacrine) to block the pro-inflammatory and adhesion-related properties of monomeric C-reactive protein (mCRP).<\/p>\n\n\n\n

Methods:<\/strong>We used three established models (platelet aggregation assay, endothelial leucocyte binding assay and monocyte inflammation via ELISA and Western blotting) to assess the potential of these therapeutics.<\/p>\n\n\n\n

Results:<\/strong>The results of this study showed that monocyte induced inflammation (raised tumor necrosis factor-alpha-TNF-a) induced by mCRP was significantly blocked in the presence of acetylcholine and nicotine, whilst tacrine and targeted antibodies (clones 8C10 and 3H12) had less of or no significant effects. Western blotting confirmed the ability of acetylcholine to inhibit mCRP-induced cell signaling phosphorylation of extracellular signal regulated kinase 1\/2 (ERK1\/2), p38 and nuclear factor-kappa B (NF-kB). There was no evidence of direct binding between small molecules and mCRP. mCRP also induced endothelial cell-monocyte adhesion in a dose dependent fashion, however, both acetylcholine and nicotine as well as targeting antibodies notably inhibited adhesion. Finally, we investigated their effects on mCRP-induced platelet aggregation. All three small molecules significantly attenuated platelet aggregation as did the antibody 8C10, although 3H12 had a weaker effect. <\/p>\n\n\n\n

Discussion:<\/strong>Acetylcholine and to a lesser extent nicotine show potential for therapeutic inhibition of mCRP-induced inflammation and cell and platelet adhesion. These results highlight the potential of targeted antibodies and small molecule therapeutics to inhibit the binding of mCRP by prevention of membrane interaction and subsequent activation of cellular cascade systems, which produce the pro-inflammatory effects associated with mCRP.<\/p>\n\n\nFull Text<\/span><\/a>","protected":false},"excerpt":{"rendered":"

Slevin, M., Lemma, R.S., Zeinolabediny, Y., Liu, D., Ferris, G.R., Caprio, V., Phillips, N., Di Napoli, M., Guo, B., Zeng, X., AlBaradie, R., Binsaleh, N.K.,\u00a0McDowell, G. & Fang, W-H. (2018) Acetylcholine inhibits monomeric C-Reactive Protein inducd inflammation, endothelial cell adhesion<\/p>\n","protected":false},"author":1,"featured_media":172,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"jetpack_post_was_ever_published":false,"_links_to":"","_links_to_target":""},"jetpack_shortlink":"https:\/\/wp.me\/P9tPlw-83","jetpack-related-posts":[{"id":121,"url":"http:\/\/clinicalbiochemistry.net\/?page_id=121","url_meta":{"origin":499,"position":0},"title":"Research Papers","date":"December 22, 2017","format":false,"excerpt":"Body, R., McDowell, G., Carley, S., Ferguson, J. & Mackway-Jones, K. (2010) \u2018Diagnosing acute myocardial infarction with troponins: how low can you go?\u2019 Emerg Med J. 27 pp. 292-296. Body, R., Carley, S., Wibberley, C., McDowell, G., Ferguson, J. & Mackway- Jones, K. (2010) \u2018The value of symptoms and signs\u2026","rel":"","context":"Similar post","img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":259,"url":"http:\/\/clinicalbiochemistry.net\/?page_id=259","url_meta":{"origin":499,"position":1},"title":"Inter-Observer Variability of H-FABP","date":"December 31, 2017","format":false,"excerpt":"Mashali, M., Norris, N., McDowell, G. & Body, R. (2016) The inter-observer reliability of a novel qualitative point of care assay for heart-type fatty acid binding protein. Clin Biochem 49 pp. 1199-1201 \u00a0 Background Heart-type fatty acid\u2013binding protein (h-FABP) may help to improve the early diagnosis of acute coronary syndromes\u2026","rel":"","context":"Similar post","img":{"alt_text":"","src":"https:\/\/i0.wp.com\/clinicalbiochemistry.net\/wp-content\/uploads\/2017\/12\/Cardiac-Marker-Test-Pages-1-300x200.png?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":549,"url":"http:\/\/clinicalbiochemistry.net\/?page_id=549","url_meta":{"origin":499,"position":2},"title":"PhD Project: BEST Study","date":"January 11, 2019","format":false,"excerpt":"Expediting the confirmation of acute myocardial infarction with point of care troponin and heart fatty acid binding protein testing to facilitate early intervention in emergency department Cardiac troponin is the reference standard biomarker for the diagnosis of acute myocardial infarction (AMI). In the appropriate clinical context, the detection of a\u2026","rel":"","context":"Similar post","img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":218,"url":"http:\/\/clinicalbiochemistry.net\/?page_id=218","url_meta":{"origin":499,"position":3},"title":"Book Chapter: ELISA Development","date":"December 27, 2017","format":false,"excerpt":"McDowell, G., Body, R., Kirwan, C., Byrne, G. & Slevin, M. (2015) \u2018A Scheme for the Development and Validation of Enzyme Linked Immunosorbent Assays (ELISA) for Measurement of Angiogenic Biomarkers in Human Blood.\u2019 In: Slevin, M. & McDowell, G. (eds.) (2015) Handbook of Vascular Biology Techniques. London: Springer pp.453-463 (10\u2026","rel":"","context":"Similar post","img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":732,"url":"http:\/\/clinicalbiochemistry.net\/?page_id=732","url_meta":{"origin":499,"position":4},"title":"Novel hs-cTn Assay with a Single Serum Test in ED.","date":"July 21, 2019","format":false,"excerpt":"3D illustration of Heart - Part of Human Organic. Objectives To evaluate diagnostic accuracy of a high-sensitivity cardiac troponin I (hs-cTnI) assay for acute coronary syndromes (ACS) in the Emergency Department (ED). The assay has high precision at low concentrations and can detect cTnI in 96.8% of healthy individuals.\u00a0 Methods\u2026","rel":"","context":"Similar post","img":{"alt_text":"","src":"https:\/\/i0.wp.com\/clinicalbiochemistry.net\/wp-content\/uploads\/2019\/07\/Screenshot-2019-07-21-at-10.53.34-e1563702957497.png?fit=364%2C500&resize=350%2C200","width":350,"height":200},"classes":[]},{"id":568,"url":"http:\/\/clinicalbiochemistry.net\/?page_id=568","url_meta":{"origin":499,"position":5},"title":"T-MACS and POCT Troponin","date":"January 17, 2019","format":false,"excerpt":"The Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid for rapid rule-in and rule-out of acute coronary syndromes using a contemporary point of care troponin assay Richard Body; Malak Almashali; Niall Morris; Phil Moss; Heather Jarman; Andrew Appelboam; Richard Parris; Louisa Chan; Alison Walker; Mark Harrison; Andrea Wootten; Garry McDowellc\u2026","rel":"","context":"Similar post","img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]}],"_links":{"self":[{"href":"http:\/\/clinicalbiochemistry.net\/index.php?rest_route=\/wp\/v2\/pages\/499"}],"collection":[{"href":"http:\/\/clinicalbiochemistry.net\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"http:\/\/clinicalbiochemistry.net\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"http:\/\/clinicalbiochemistry.net\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/clinicalbiochemistry.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=499"}],"version-history":[{"count":3,"href":"http:\/\/clinicalbiochemistry.net\/index.php?rest_route=\/wp\/v2\/pages\/499\/revisions"}],"predecessor-version":[{"id":583,"href":"http:\/\/clinicalbiochemistry.net\/index.php?rest_route=\/wp\/v2\/pages\/499\/revisions\/583"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/clinicalbiochemistry.net\/index.php?rest_route=\/wp\/v2\/media\/172"}],"wp:attachment":[{"href":"http:\/\/clinicalbiochemistry.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=499"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}