Complement activation in vitro by the red cell substitute, liposome- encapsulated hemoglobin: Mechanism of activation and inhibition by soluble complement receptor type 1

J. Szebeni, N. M. Wassef, K. R. Hartman, A. S. Rudolph, C. R. Alving

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

BACKGROUND: Liposome-encapsulated hemoglobin (LEH) has been developed as an emergency blood substitute, yet its effect on human complement has never been explored. Considering that complement activation is a major pathogenic factor in the respiratory distress syndrome that often develops in trauma and shock, LEH-induced complement activation may be a critical safety issue. STUDY DESIGN AND METHODS: Various LEH and corresponding empty liposomes were incubated with normal human sera, and various markers of complement activation (serum levels of C4d, Bb, SCSb-9, and CH 50; C5a-induced granulocyte aggregation; membrane deposition of C3b) were measured. Incubations were also performed in the presence of (ethylene- bis[oxyethylenenitrilo]tetraacetic acid) (EGTA) and Mg ++ (EGTA/Mg ++) and soluble complement receptor type 1. RESULTS: LEH and liposomes activated human complement, as indicated by significant changes in one or more markers. The effect was primarily due to the presence of the phospholipid vehicle; small, unilamellar, highly homodispersed vesicles induced the greatest degree of complement activation. Complement activation was partially inhibited by EGTA/Mg ++. The latter finding, together with the parallel increases in serum C4d and Bb, suggests activation of both the classical and alternative pathways. Soluble complement receptor type 1 (0.05-20 μg/mL) efficiently inhibited all vesicle-induced complement activation. CONCLUSION: Because of complement activation, the use of LEH for transfusion may require careful evaluation of safety. Soluble complement receptor type 1 may be useful as a prophylactic agent for complement activation-related complications of liposome infusions.

Original languageEnglish
Pages (from-to)150-159
Number of pages10
JournalTransfusion
Volume37
Issue number2
Publication statusPublished - Feb 1997

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Blood Substitutes
Complement Receptors
Complement Activation
Liposomes
Hemoglobins
Egtazic Acid
Complement Hemolytic Activity Assay
Safety
In Vitro Techniques
Serum
Granulocytes
Shock
Phospholipids
Emergencies
Biomarkers
Acids
Membranes
Wounds and Injuries

ASJC Scopus subject areas

  • Hematology
  • Immunology

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Complement activation in vitro by the red cell substitute, liposome- encapsulated hemoglobin : Mechanism of activation and inhibition by soluble complement receptor type 1. / Szebeni, J.; Wassef, N. M.; Hartman, K. R.; Rudolph, A. S.; Alving, C. R.

In: Transfusion, Vol. 37, No. 2, 02.1997, p. 150-159.

Research output: Contribution to journalArticle

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