@article{MTMT:30786516,
title = {Pseudo-anaphylaxis to Polyethylene Glycol (PEG)-Coated Liposomes: Roles of Anti-PEG IgM and Complement Activation in a Porcine Model of Human Infusion Reactions},
url = {https://m2.mtmt.hu/api/publication/30786516},
author = {Kozma, Gergely Tibor and Mészáros, Tamás and Vashegyi, Ildikó and Fülöp, Tamás and Őrfi, Erik and Dézsi, László and Rosivall, László and Bavli, Yaelle and Urbanics, Rudolf and Mollnes, Tom Eirik and Barenholz, Yechezkel and Szebeni, János},
doi = {10.1021/acsnano.9b03942},
journal-iso = {ACS NANO},
journal = {ACS NANO},
volume = {13},
unique-id = {30786516},
issn = {1936-0851},
year = {2019},
eissn = {1936-086X},
pages = {9315-9324},
orcid-numbers = {Mészáros, Tamás/0000-0002-4190-9793; Vashegyi, Ildikó/0000-0002-4190-9793; Fülöp, Tamás/0000-0003-2889-1370; Őrfi, Erik/0000-0002-2190-0708; Dézsi, László/0000-0002-4190-9793; Rosivall, László/0000-0002-9809-3879; Bavli, Yaelle/0000-0002-4190-9793; Urbanics, Rudolf/0000-0002-4190-9793; Mollnes, Tom Eirik/0000-0002-4190-9793; Barenholz, Yechezkel/0000-0002-4190-9793}
}
@article{MTMT:30466738,
title = {Acute physiological changes caused by complement activators and amphotericin B-containing liposomes in mice},
url = {https://m2.mtmt.hu/api/publication/30466738},
author = {Őrfi, Erik and Mészáros, Tamás and Hennies, Mark and Fülöp, Tamás and Dézsi, László and Nardocci, Alexander and Rosivall, László and Hamar, Péter and Neun, Barry W. and Dobrovolskaia, Marina A. and Szebeni, János and Szénási, Gábor},
doi = {10.2147/IJN.S187139},
journal-iso = {INT J NANOMED},
journal = {INTERNATIONAL JOURNAL OF NANOMEDICINE},
volume = {14},
unique-id = {30466738},
issn = {1176-9114},
year = {2019},
eissn = {1178-2013},
pages = {1563-1573},
orcid-numbers = {Őrfi, Erik/0000-0002-2190-0708; Hennies, Mark/0000-0002-5004-8120; Fülöp, Tamás/0000-0003-2889-1370; Dézsi, László/0000-0002-4190-9793; Rosivall, László/0000-0002-9809-3879; Hamar, Péter/0000-0002-1095-3564; Dobrovolskaia, Marina A./0000-0002-4233-9227; Szebeni, János/0000-0003-1738-797X; Szénási, Gábor/0000-0002-7350-6091}
}
@article{MTMT:3377436,
title = {Mechanism of nanoparticle-induced hypersensitivity in pigs: complement or not complement?},
url = {https://m2.mtmt.hu/api/publication/3377436},
author = {Szebeni, János},
doi = {10.1016/j.drudis.2018.01.025},
journal-iso = {DRUG DISCOV TODAY},
journal = {DRUG DISCOVERY TODAY},
volume = {23},
unique-id = {3377436},
issn = {1359-6446},
abstract = {A recent study on nanoparticle-induced hypersensitivity reactions in pigs showed robust pulmonary intravascular macrophage clearance of Polybead (R) carboxylate microspheres in mediating the adverse cardiopulmonary distress, irrespective of the ability of these particles to activate the complement (C) system in vitro. Focusing on this observation, this article highlights the controversies in projecting in vitro C assay data to in vivo conditions and applying data on polystyrene particles to therapeutic nanopharmaceuticals. Based on overwhelming evidence of a role of anaphylatoxins in hypersensitivity reactions, the need to further explore the role of C activation in the reported and other reactions is highlighted. C-activation-related and C-independent pseudoallergies (CARPA and CIPA) can proceed simultaneously, as outlined by the 'double-hit' hypothesis.},
keywords = {Cardiopulmonary distress; Infusion reactions; Immune toxicity; INTRAVENOUS IRON; ACTIVATION-RELATED PSEUDOALLERGY; PEGYLATED LIPOSOMAL DOXORUBICIN; PORCINE CARPA; ABC PHENOMENON; CARDIAC ANAPHYLAXIS; ACCELERATED BLOOD CLEARANCE},
year = {2018},
eissn = {1878-5832},
pages = {487-492}
}
@article{MTMT:30473882,
title = {Roadmap and strategy for overcoming infusion reactions to nanomedicines},
url = {https://m2.mtmt.hu/api/publication/30473882},
author = {Szebeni, János and Simberg, Dmitri and Gonzalez-Fernandez, Africa and Barenholz, Yechezkel and Dobrovolskaia, Marina A.},
doi = {10.1038/s41565-018-0273-1},
journal-iso = {NAT NANOTECHNOL},
journal = {NATURE NANOTECHNOLOGY},
volume = {13},
unique-id = {30473882},
issn = {1748-3387},
abstract = {Infusion reactions (IRs) are complex, immune-mediated side effects that mainly occur within minutes to hours of receiving a therapeutic dose of intravenously administered pharmaceutical products. These products are diverse and include both traditional pharmaceuticals (for example biological agents and small molecules) and new ones (for example nanotechnology-based products). Although IRs are not unique to nanomedicines, they represent a hurdle for the translation of nanotechnology-based drug products. This Perspective offers a big picture of the pharmaceutical field and examines current understanding of mechanisms responsible for IRs to nanomedicines. We outline outstanding questions, review currently available experimental evidence to provide some answers and highlight the gaps. We review advantages and limitations of the in vitro tests and animal models used for studying IRs to nanomedicines. Finally, we propose a roadmap to improve current understanding, and we recommend a strategy for overcoming the problem.},
year = {2018},
eissn = {1748-3395},
pages = {1100-1108},
orcid-numbers = {Gonzalez-Fernandez, Africa/0000-0002-9226-4825}
}
@article{MTMT:30473881,
title = {Animal models for analysis of immunological responses to nanomaterials: Challenges and considerations},
url = {https://m2.mtmt.hu/api/publication/30473881},
author = {Zamboni, William C. and Szebeni, János and Kozlov, Serguei V. and Lucas, Andrew T. and Piscitelli, Joseph A. and Dobrovolskaia, Marina A.},
doi = {10.1016/j.addr.2018.09.012},
journal-iso = {ADV DRUG DELIV REV},
journal = {ADVANCED DRUG DELIVERY REVIEWS},
volume = {136},
unique-id = {30473881},
issn = {0169-409X},
abstract = {Nanotechnology provides many solutions to improve conventional drug delivery and has a unique niche in the areas related to the specific targeting of the immune system, such as immunotherapies and vaccines. Preclinical studies in this field rely heavily on the combination of in vitro and in vivo methods to assess the safety and efficacy of nanotechnology platforms, nanoparticle-formulated drugs, and vaccines. While certain types of toxicities can be evaluated in vitro and good in vitro-in vivo correlation has been demonstrated for such tests, animal studies are still needed to address complex biological questions and, therefore, provide a unique contribution to establishing nanoparticle safety and efficacy profiles. The genetic, metabolic, mechanistic, and phenotypic diversity of currently available animal models often complicates both the animal choice and the interpretation of the results. This review summarizes current knowledge about differences in the immune system function and immunological responses of animals commonly used in preclinical studies of nanomaterials. We discuss challenges, highlight current gaps, and propose recommendations for animal model selection to streamline preclinical analysis of nanotechnology formulations. (C) 2018 Elsevier B.V. All rights reserved.},
keywords = {Animals; Inflammation; MACROPHAGES; COMPLEMENT; NANOPARTICLES; Allergy; Anaphylaxis; cytokine storm; MPS},
year = {2018},
eissn = {1872-8294},
pages = {82-96}
}
@article{MTMT:3330122,
title = {Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes},
url = {https://m2.mtmt.hu/api/publication/3330122},
author = {Wibroe, PP and Anselmo, AC and Nilsson, PH and Sarode, A and Gupta, V and Urbanics, R and Szebeni, János and Hunter, AC and Mitragotri, S and Mollnes, TE and Moghimi, SM},
doi = {10.1038/NNANO.2017.47},
journal-iso = {NAT NANOTECHNOL},
journal = {NATURE NANOTECHNOLOGY},
volume = {12},
unique-id = {3330122},
issn = {1748-3387},
abstract = {Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust pulmonary intravascular macrophage clearance of nanoparticles in mediating adverse cardiopulmonary distress in pigs irrespective of complement activation. Specifically, we show that delaying particle recognition by macrophages within the first few minutes of injection overcomes adverse reactions in pigs using two independent approaches. First, we changed the particle geometry from a spherical shape (which triggers cardiopulmonary distress) to either rod-or disk-shape morphology. Second, we physically adhered spheres to the surface of erythrocytes. These strategies, which are distinct from commonly leveraged stealth engineering approaches such as nanoparticle surface functionalization with poly(ethylene glycol) and/or immunological modulators, prevent robust macrophage recognition, resulting in the reduction or mitigation of adverse cardiopulmonary distress associated with nanopharmaceutical administration.},
year = {2017},
eissn = {1748-3395},
pages = {589-594}
}
@article{MTMT:2745559,
title = {Features of complement activation-related pseudoallergy to liposomes with different surface charge and PEGylation: Comparison of the porcine and rat responses},
url = {https://m2.mtmt.hu/api/publication/2745559},
author = {Dézsi, László and Fülöp, Tamás and Mészáros, Tamás and Szénási, Gábor and Urbanics, R and Vázsonyi, C and Őrfi, Erik and Rosivall, László and Nemes, R and Kok, RJ and Metselaar, JM and Storm, G and Szebeni, János},
doi = {10.1016/j.jconrel.2014.08.009},
journal-iso = {J CONTROL RELEASE},
journal = {JOURNAL OF CONTROLLED RELEASE},
volume = {195},
unique-id = {2745559},
issn = {0168-3659},
abstract = {Pigs are known to provide a sensitive model for studying complement (C) activation-related pseudoallergy (CARPA), a hypersensitivity reaction to liposomal and many other nanomedicines that limits their clinical use. The utility of rats as a CARPA model has, however, not been analyzed to date in detail. The present study compared the two models by inducing CARPA with i.v. bolus injections of two reactogenic liposomes that differed from each other in surface properties: one was AmBisome, a strong anionic, free-surface small unilamellar liposome (SUV), while the other was neutral, polyethylene glycol (PEG)-grafted SUV wherein the 2 kDa-PEG was anchored to the membrane via cholesterol (Chol-PEG). Both in pigs and rats AmBisome caused significant consumption of C3, indicating C activation, along with paralleling massive changes in blood pressure, white blood cell, platelet counts and in plasma thromboxane B2 levels, indicating CARPA. These processes were similar in the two species in terms of kinetics, but significantly differed in the doses that caused major hemodynamic changes (~ 0.01 and ~ 22 mg phospholipid (PL)/kg in pigs and rats, respectively). Pigs responded to AmBisome with pulmonary hypertension and systemic hypotension, and the reaction was not tachyphylactic. The major response of rats was systemic hypotension, leukopenia followed by leukocytosis, and thrombocytopenia. Chol-PEG liposomes caused severe reaction in pigs at 0.1 mg/kg, while the reaction they caused in rats was mild even at 300 mg PL/kg. Importantly, the reaction to Chol-PEG in pigs was partly tachyphylactic. These observations highlight fundamental differences in the immune mechanisms of porcine and rat CARPA, and also show a major impact of liposome surface characteristics, determining the presence or absence of tachyphylaxis. The data suggest that rats are 2-3 orders of magnitude less sensitive to liposomal CARPA than pigs; however, the causes of these differences, the PEG-dependent tachyphylaxis and the massive reactivity of Chol-PEG liposomes remain unclear. © 2014 Elsevier B.V. All rights reserved.},
keywords = {Nanomedicines; Pseudoallergy; Anaphylaxis; Anaphylatoxins; CARPA; Adverse drug effects},
year = {2014},
eissn = {1873-4995},
pages = {2-10},
orcid-numbers = {Dézsi, László/0000-0002-4190-9793; Fülöp, Tamás/0000-0003-2889-1370; Szénási, Gábor/0000-0002-7350-6091; Őrfi, Erik/0000-0002-2190-0708; Rosivall, László/0000-0002-9809-3879}
}
@article{MTMT:2748955,
title = {Complement activation-related pseudoallergy: A stress reaction in blood triggered by nanomedicines and biologicals},
url = {https://m2.mtmt.hu/api/publication/2748955},
author = {Szebeni, János},
doi = {10.1016/j.molimm.2014.06.038},
journal-iso = {MOL IMMUNOL},
journal = {MOLECULAR IMMUNOLOGY},
volume = {61},
unique-id = {2748955},
issn = {0161-5890},
abstract = {Intravenous injection of a variety of nanotechnology enhanced (liposomal, micellar, polymer-conjugated) and protein-based (antibodies, enzymes) drugs can lead to hypersensitivity reactions (HSRs), also known as infusion, or anaphylactoid reactions. The molecular mechanism of mild to severe allergy symptoms may differ from case to case and is mostly not known, however, in many cases a major cause, or contributing factor is activation of the complement (C) system. The clinical relevance of C activation-related HSRs, a non-IgE-mediated pseudoallergy (CARPA), lies in its unpredictability and occasional lethal outcome. Accordingly, there is an unmet medical need to develop laboratory assays and animal models that quantitate CARPA. This review provides basic information on CARPA; a short history, issues of nomenclature, incidence, classification of reactogenic drugs and symptoms, and the mechanisms of C activation via different pathways. It is pointed out that anaphylatoxin-induced mast cell release may not entirely explain the severe reactions; a "second hit" on allergy mediating cells may also contribute. In addressing the increasing requirements for CARPA testing, the review evaluates the available assays and animal models, and proposes a possible algorithm for the screening of reactogenic drugs and hypersensitive patients. Finally, an analogy is proposed between CARPA and the classic stress reaction, suggesting that CARPA represents a "blood stress" reaction, a systemic fight of the body against harmful biological and chemical agents via the anaphylatoxin/mast-cell/circulatory system axis, in analogy to the body's fight of physical and emotional stress via the hypothalamo/pituitary/adrenal axis. In both cases the response to a broad variety of noxious effects are funneled into a uniform pattern of physiological changes. © 2014 Elsevier Ltd. All rights reserved.},
keywords = {Allergy; Pseudoallergy; Anaphylaxis; Anaphylatoxins; inflammatory mediators; CARPA},
year = {2014},
eissn = {1872-9142},
pages = {163-173}
}
@article{MTMT:2502607,
title = {Complement activation by PEGylated liposomes containing prednisolone},
url = {https://m2.mtmt.hu/api/publication/2502607},
author = {Van, Den Hoven JM and Nemes, R and Metselaar, JM and Nuijen, B and Beijnen, JH and Storm, G and Szebeni, János},
doi = {10.1016/j.ejps.2013.03.007},
journal-iso = {EUR J PHARM SCI},
journal = {EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES},
volume = {49},
unique-id = {2502607},
issn = {0928-0987},
abstract = {Infusion of PEGylated liposomes can give rise to hypersensitivity reactions (HSRs) in a relatively large number of patients. Previously it has been shown that these reactions can be caused by activation of the complement (C) system by a negative charge on the anchor molecule of PEG at the liposomal surface. In this study it is tested whether the activation of the C system by PEG-liposomes could be significantly reduced to values comparable to nonreactive liposomal formulations, by changing the PEGylation-profile on the liposomal surface. Therefore, the formation of C activation markers SC5b-9, C3a, C4d and Bb in normal human serum by both prednisolone loaded and empty liposomes with a variation of PEG chain length, PEG surface concentration, PEG anchor molecule and liposomal size was determined using in vitro assays. The tested liposomes caused no or only mild (30%) activation of C except for one formulation wherein the PEG2000 was anchored to cholesterol (CHOL-PEG2000). The latter liposomes caused paralleling rises in SC5b-9 and Bb levels, suggesting excess activation of the alternative pathway. While the relative safety of weak C activator liposomes remains to be confirmed in vivo, the unique, non-charge and non-antibody-mediated direct conversion of C3 by CHOL-PEG2000 liposomes (although argues against the clinical development of these vesicles) opens new opportunities to understand liposomal C activation at the molecular level. © 2013 Elsevier B.V. All rights reserved.},
keywords = {Humans; SERUM; COMPLEMENT; ARTICLE; LIPIDS; HYPERSENSITIVITY REACTIONS; COMPLEMENT ACTIVATION; human; Anti-Inflammatory Agents; priority journal; enzyme linked immunosorbent assay; normal human; Prednisolone; Polyethylene Glycols; cholesterol; unclassified drug; pegylated liposome; Liposomes; complement component sc5b 9; complement component C4d; complement component C3a; complement component bb; Liposome; Macrogol 2000; Infusion reactions; PEGylated liposomes},
year = {2013},
eissn = {1879-0720},
pages = {265-271}
}
@article{MTMT:1303884,
title = {Complement-Dependent Shock and Tissue Damage Induced by Intravenous Injection of Cholesterol-Enriched Liposomes in Rats},
url = {https://m2.mtmt.hu/api/publication/1303884},
author = {Baranyi, L and Szebeni, János and Sávay, S and Bodo, Mihaly and Basta, M and Bentley, T B and Bunger, R and Alving, C R},
journal-iso = {J APPLIED RES},
journal = {JOURNAL OF APPLIED RESEARCH: IN CLINICAL AND EXPERIMENTAL THERAPEUTICS},
volume = {3},
unique-id = {1303884},
issn = {1537-064X},
abstract = {A single intravenous injection of 4 to 8 mg/kg of large, multilamellar, cholesterol-enriched lipid vesicles (containing 71% cholesterol; HC-MLV) induced marked bradycardia, arrhythmia, and transient decrease in systemic blood pressure in rats. A single higher dose (15-20 mg/kg), or repeated injections of 4 to 8 mg/kg HC-MLV, resulted in severe pulmonary hemorrhage and edema (ARDS-like histologic changes), systemic microthrombus formation, hemorrhage in the kidneys and liver, as well as early signs of diffuse myocardial damage. Complement depletion with cobra venom factor, or the use of thromboxane A2 receptor inhibitor (SQ30741), prevented these adverse reactions, pointing to the involvement of C activation and TXA2 release in the pathomechanism. The likely role of C activation was supported by the demonstration of strong C activation by HC-MLV in rat serum in vitro, along with the binding of natural IgG and IgM antibodies to these vesicles. The C activation by HC-MLV seems to proceed by way of the classic pathway mediated by natural antilipid antibodies. These studies present a novel, powerful method for inducing anaphylactoid shock and other C activation-related pathologic changes providing a model for multiple organ failure, semicrystalline cholesterol embolism, and C activation-related pseudoallergy.},
keywords = {Female; HEMORRHAGE; ARTICLE; COMPLEMENT ACTIVATION; controlled study; immunoglobulin G antibody; nonhuman; animal tissue; animal model; Histopathology; in vitro study; Flow Cytometry; heart arrhythmia; immunoglobulin M antibody; cholesterol; hypotension; tissue injury; particle size; multiple organ failure; microthrombus; lung hemorrhage; liver hemorrhage; kidney hemorrhage; hemodynamic monitoring; heart muscle injury; antigen binding; cobrotoxin; 7 [3 [(2 heptanamidoacetamido)methyl] 7 oxabicyclo[2.2.1]hept 2 yl] 5 heptenoic acid; Thrombus; DIC; C5a; thromboxane A2; edema; drug carrier; bradycardia; Allergy; shock; anaphylactic shock; Liposome; rat},
year = {2003},
pages = {221-231}
}
@article{MTMT:1303883,
title = {Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil®): Possible role in hypersensitivity reactions},
url = {https://m2.mtmt.hu/api/publication/1303883},
author = {Chanan-Khan, A and Szebeni, János and Savay, S and Liebes, L and Rafique, N M and Alving, C R and Muggia, F M},
doi = {10.1093/annonc/mdg374},
journal-iso = {ANN ONCOL},
journal = {ANNALS OF ONCOLOGY},
volume = {14},
unique-id = {1303883},
issn = {0923-7534},
abstract = {Background: Pegylated liposomal doxorubicin (Doxil®) has been reported to cause immediate hypersensitivity reactions (HSRs) that cannot be explained as IgE-mediated (type I) allergy. Previous in vitro and animal studies indicated that activation of the complement (C) system might play a causal role in the process, a proposal that has not been tested in humans to date. Patients and methods: Patients with solid tumors (n = 29) treated for the first time with Doxil were evaluated for HSRs and concurrent C activation. HSRs were classified from mild to severe, while C activation was estimated by serial measurement of plasma C terminal complex (SC5b-9) levels. Increases in SC5b-9 were compared in patients with or without reactions, and were correlated with Doxil dose rate. Results: Moderate to severe HSRs occurred in 45% of patients. Plasma SC5b-9 at 10 min after infusion was significantly elevated in 92% of reactor patients versus 56% in the non-reactor group, and the rise was greater in reactors than in non-reactors. We found significant association between C activation and HSRs, both showing direct correlation with the initial Doxil dose rate. Conclusions: C activation may play a key role in HSRs to Doxil. However, low-level C activation does not necessarily entail clinical symptoms, highlighting the probable involvement of further, as yet unidentified, amplification factors.},
keywords = {Aged; Adult; Female; Middle Aged; Male; Humans; ARTICLE; CIMETIDINE; HYPERSENSITIVITY REACTIONS; COMPLEMENT ACTIVATION; human; disease association; steroid; priority journal; controlled study; Dose-Response Relationship, Drug; dose response; disease severity; clinical article; controlled clinical trial; clinical trial; drug formulation; antihistaminic agent; hydrocortisone; Neoplasms; Hypersensitivity, Immediate; symptomatology; medical assessment; disease classification; correlation function; complement blood level; tropisetron; protein S; ondansetron; complement membrane attack complex; diphenhydramine; solid tumor; Antibiotics, Antineoplastic; Cancer chemotherapy; Allergy; hypersensitivity reaction; drug hypersensitivity; Liposomes; Anaphylatoxins; doxorubicin; Liposome},
year = {2003},
eissn = {1569-8041},
pages = {1430-1437}
}
@article{MTMT:1303902,
title = {Complement activation and thromboxane secretion by liposome-encapsulated hemoglobin in rats in vivo: Inhibition by soluble complement receptor type 1},
url = {https://m2.mtmt.hu/api/publication/1303902},
author = {Szebeni, János and Spielberg, H and Cliff, R O and Wassef, N M and Rudolph, A S and Alving, C R},
doi = {10.3109/10731199709118925},
journal-iso = {ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY},
journal = {ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY},
volume = {25},
unique-id = {1303902},
issn = {1073-1199},
abstract = {Intravenous administration of liposome-encapsulated hemoglobin (LEH) in rats led to an early (within 15 min) decline of hemolytic complement (C) activity in the plasma along with a significant, parallel rise in thromboxane B2 (TXB2) levels. The TXB2 response was inhibited by co-administration of soluble C receptor type 1 (sCR1) with LEH, as well as by C depletion with cobra venom factor. These observations provide evidence for a causal relationship between LEH-induced C activation and TXB2 release, and suggest that sCR1 could be useful in attenuating the acute respiratory, hematological and hemodynamic side effects of LEH described earlier in the rat. Intravenous administration of liposome-encapsulated hemoglobin (LEH) in rats led to an early (within 15 min) decline of hemolytic complement (C) activity in the plasma along with a significant, parallel rise in thromboxane B2 (TXB2) levels. The TXB2 response was inhibited by co-administration of soluble C receptor type 1 (sCR1) with LEH, as well as by C depletion with cobra venom factor. These observations provide evidence for a causal relationship between LEH-induced C activation and TXB2 release, and suggest that sCR1 could be useful in attenuating the acute respiratory, hematological and hemodynamic side effects of LEH described earlier in the rat.},
keywords = {Animals; Female; THROMBOXANE; RATS; ARTICLE; COMPLEMENT ACTIVATION; Rats, Sprague-Dawley; controlled study; HEMOGLOBIN; nonhuman; animal experiment; Animalia; Drug Synergism; Hemodynamics; Injections, Intravenous; Solubility; Liposomes encapsulated hemoglobin; Complement Inactivator Proteins; Receptors, Complement; Living systems studies; encapsulation; Hemoglobins; Blood Substitutes; cobrotoxin; complement component C3b receptor; thromboxane B2; Liposomes; Liposome; rat},
year = {1997},
eissn = {1532-4184},
pages = {347-355}
}
@article{MTMT:1303911,
title = {Complement activation in rats by liposomes and liposome-encapsulated hemoglobin: Evidence for anti-lipid antibodies and alternative pathway activation},
url = {https://m2.mtmt.hu/api/publication/1303911},
author = {Szebeni, János and Wassef, N M and Spielberg, H and Rudolph, A S and Alving, C R},
doi = {10.1006/bbrc.1994.2658},
journal-iso = {BIOCHEM BIOPH RES CO},
journal = {BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS},
volume = {205},
unique-id = {1303911},
issn = {0006-291X},
abstract = {Intravenous injection of hemoglobin-containing liposomes (LEH) caused a significant reduction in plasma hemolytic complement activity in rats on a time scale of minutes. Liposomes without hemoglobin also caused complement consumption, but less than LEH, while free hemoglobin was without effect. Consistent with complement activation, the LEH-induced drop in plasma hemolytic complement activity was closely paralleled by an increase in plasma thromboxane B2 level. Studies to determine the mechanism of complement activation demonstrated the presence of natural antibodies in rat serum against all lipid components of LEH, thus, the potential for classical pathway activation. Yet, in vitro incubation of LEH with rat serum showed that: 1) EGTA/Mg++, which inhibits complement activation through the classical pathway, did not inhibit complement consumption of LEH, and 2) the use of serum preheated at 50°C, which inhibits C activation through the alternative pathway by selectively depleting factor B, effectively reversed the complement-consuming effect of LEH. Consequently, LEH-induced complement activation in rat serum seems to involve primarily the alternative pathway.},
keywords = {Female; RATS; ARTICLE; LIPIDS; ANTIBODIES; COMPLEMENT ACTIVATION; animal; Rats, Sprague-Dawley; priority journal; controlled study; HEMOGLOBIN; nonhuman; animal experiment; Support, Non-U.S. Gov't; intravenous drug administration; unclassified drug; Support, U.S. Gov't, Non-P.H.S.; lipid antibody; complement alternative pathway; Hemoglobins; Complement Pathway, Classical; egtazic acid; Liposomes; Complement Pathway, Alternative; Liposome; rat},
year = {1994},
eissn = {1090-2104},
pages = {255-263}
}