Complement-Dependent Shock and Tissue Damage Induced by Intravenous Injection of Cholesterol-Enriched Liposomes in Rats

Lajos Baranyi, János Szebeni, Sándor Sávay, Michael Bodo, Milan Basta, Timothy B. Bentley, Rolf Bunger, Carl R. Alving

Research output: Article

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)221-231
Number of pages11
JournalJournal of Applied Research
Volume3
Issue number3
Publication statusPublished - jún. 1 2003

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Baranyi, L., Szebeni, J., Sávay, S., Bodo, M., Basta, M., Bentley, T. B., Bunger, R., & Alving, C. R. (2003). Complement-Dependent Shock and Tissue Damage Induced by Intravenous Injection of Cholesterol-Enriched Liposomes in Rats. Journal of Applied Research, 3(3), 221-231.