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

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

Research output: Contribution to journalArticle

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 - Jun 2003

Fingerprint

Liposomes
Intravenous Injections
Shock
Cholesterol Embolism
Cholesterol
Prostaglandin H2 Receptors Thromboxane A2
Hemorrhage
Multiple Organ Failure
Antibodies
Pulmonary Edema
Bradycardia
Immunoglobulin M
Cardiac Arrhythmias
Immunoglobulin G
Blood Pressure
Kidney
Lipids
Injections
Liver
Serum

Keywords

  • C5a
  • Cholesterol
  • Complement activation
  • DIC
  • Edema
  • Hemorrhage
  • Liposome
  • Shock
  • Thromboxane A2
  • Thrombus

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology

Cite this

Baranyi, L., Szebeni, J., Sávay, S., Bodo, M., Basta, M., Bentley, T. B., ... 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.

Complement-Dependent Shock and Tissue Damage Induced by Intravenous Injection of Cholesterol-Enriched Liposomes in Rats. / Baranyi, Lajos; Szebeni, J.; Sávay, Sándor; Bodo, Michael; Basta, Milan; Bentley, Timothy B.; Bunger, Rolf; Alving, Carl R.

In: Journal of Applied Research, Vol. 3, No. 3, 06.2003, p. 221-231.

Research output: Contribution to journalArticle

Baranyi, L, Szebeni, J, Sávay, S, Bodo, M, Basta, M, Bentley, TB, Bunger, R & Alving, CR 2003, 'Complement-Dependent Shock and Tissue Damage Induced by Intravenous Injection of Cholesterol-Enriched Liposomes in Rats', Journal of Applied Research, vol. 3, no. 3, pp. 221-231.
Baranyi, Lajos ; Szebeni, J. ; Sávay, Sándor ; Bodo, Michael ; Basta, Milan ; Bentley, Timothy B. ; Bunger, Rolf ; Alving, Carl R. / Complement-Dependent Shock and Tissue Damage Induced by Intravenous Injection of Cholesterol-Enriched Liposomes in Rats. In: Journal of Applied Research. 2003 ; Vol. 3, No. 3. pp. 221-231.
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