{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T18:17:35Z","timestamp":1784571455462,"version":"3.55.0"},"reference-count":24,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T00:00:00Z","timestamp":1567987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002332","name":"Semmelweis Egyetem","doi-asserted-by":"publisher","award":["EFOP-3.6.3-VEKOP-16-2017-00009"],"award-info":[{"award-number":["EFOP-3.6.3-VEKOP-16-2017-00009"]}],"id":[{"id":"10.13039\/501100002332","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Seventh Framework Programme","award":["#309820"],"award-info":[{"award-number":["#309820"]}]},{"name":"Seventh Framework Programme","award":["#602923"],"award-info":[{"award-number":["#602923"]}]},{"DOI":"10.13039\/501100010024","name":"Hungarian Science Foundation","doi-asserted-by":"publisher","award":["K-113164"],"award-info":[{"award-number":["K-113164"]}],"id":[{"id":"10.13039\/501100010024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011748","name":"Phospholipid Research Center","doi-asserted-by":"publisher","award":["not known"],"award-info":[{"award-number":["not known"]}],"id":[{"id":"10.13039\/501100011748","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Complement (C) activation can underlie the infusion reactions to liposomes and other nanoparticle-based medicines, a hypersensitivity syndrome that can be partially reproduced in animal models. However, the sensitivities and manifestations substantially differ in different species, and C activation may not be the only cause of pathophysiological changes. In order to map the species variation of C-dependent and -independent pseudoallergy (CARPA\/CIPA), here we used known C activators and C activator liposomes to compare their acute hemodynamic, hematological, and biochemical effects in rats. These C activators were cobra venom factor (CVF), zymosan, AmBisome (at 2 doses), its amphotericin B-free vehicle (AmBisombo), and a PEGylated cholesterol-containing liposome (PEG-2000-chol), all having different powers to activate C in rat blood. The pathophysiological endpoints measured were blood pressure, leukocyte and platelet counts, and plasma thromboxane B2, while C activation was assessed by C3 consumption using the Pan-Specific C3 assay. The results showed strong linear correlation between C activation and systemic hypotension, pointing to a causal role of C activation in the hemodynamic changes. The observed thrombocytopenia and leukopenia followed by leukocytosis also correlated with C3 conversion in case of C activators, but not necessarily with C activation by liposomes. These findings are consistent with the double hit hypothesis of hypersensitivity reactions (HSRs), inasmuch as strong C activation can fully account for all symptoms of HSRs, but in case of no-, or weak C activators, the pathophysiological response, if any, is likely to involve other activation pathways.<\/jats:p>","DOI":"10.3390\/molecules24183283","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T11:26:17Z","timestamp":1568028377000},"page":"3283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Complement Activation-Related Pathophysiological Changes in Anesthetized Rats: Activator-Dependent Variations of Symptoms and Mediators of Pseudoallergy"],"prefix":"10.3390","volume":"24","author":[{"given":"L\u00e1szl\u00f3","family":"D\u00e9zsi","sequence":"first","affiliation":[{"name":"Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"M\u00e9sz\u00e1ros","sequence":"additional","affiliation":[{"name":"SeroScience LCC., 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"\u0150rfi","sequence":"additional","affiliation":[{"name":"Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"F\u00fcl\u00f6p","sequence":"additional","affiliation":[{"name":"Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hennies","sequence":"additional","affiliation":[{"name":"TECO Development GmbH, 53359 Rheinbach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Rosivall","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"},{"name":"Nephrology Center, Institute of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1095-3564","authenticated-orcid":false,"given":"P\u00e9ter","family":"Hamar","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary"},{"name":"Institute for Translational Medicine, Medical School, University of P\u00e9cs, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Szebeni","sequence":"additional","affiliation":[{"name":"Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"},{"name":"SeroScience LCC., 1089 Budapest, Hungary"},{"name":"Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, 3505 Miskolc, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Sz\u00e9n\u00e1si","sequence":"additional","affiliation":[{"name":"SeroScience LCC., 1089 Budapest, Hungary"},{"name":"Institute of Translational Medicine, Semmelweis University, 1089 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ijpharm.2018.01.037","article-title":"Liquid crystalline drug delivery vehicles for oral and IV\/subcutaneous administration of poorly soluble (and soluble) drugs","volume":"539","author":"Otte","year":"2018","journal-title":"Int. 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