Complement activation in rats by liposomes and liposome-encapsulated hemoglobin: Evidence for anti-lipid antibodies and alternative pathway activation

Janos Szebeni, Nabila M. Wassef, Helmut Spielberg, Alan S. Rudolph, Carl R. Alving

Research output: Article

53 Citations (Scopus)

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 by 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, LEI-induced complement activation in rat serum seems to involve primarily the alternative pathway.

Original languageEnglish
Pages (from-to)255-263
Number of pages9
JournalBiochemical and biophysical research communications
Volume205
Issue number1
DOIs
Publication statusPublished - nov. 30 1994

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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