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Heparin and modified heparin inhibit complement activation in vivo
J M Weiler1, R E Edens, R J Linhardt
1Iowa City Veterans Administration Medical Center, IA.
Journal of Immunology (Baltimore, Md. : 1950)
|May 15, 1992
Summary
Commercial heparin and modified heparin (Hep-NAc) effectively inhibit complement (C) activation in vivo, even with reduced anticoagulant properties. This finding supports developing new drugs to regulate C system activity.
Area of Science:
- Immunology
- Pharmacology
- Biochemistry
Background:
- Heparin is known to regulate complement (C) activity in vitro.
- Its in vivo efficacy in modulating C activation has not been extensively studied.
- Derivatized heparin (Hep-NAc) possesses diminished anticoagulant properties.
Purpose of the Study:
- To investigate the in vivo efficacy of commercial heparin and Hep-NAc in inhibiting complement activation.
- To assess the impact of these heparins on complement-mediated hemolysis induced by cobra venom factor.
Main Methods:
- Guinea pigs were pretreated with either heparin, Hep-NAc, or saline.
- Complement activation was induced using cobra venom factor.
- Blood samples were analyzed for total hemolytic C, C3 hemolytic activity, free hemoglobin, and activated partial thromboplastin time.
Main Results:
- Both heparin and Hep-NAc significantly slowed the decrease in total hemolytic C and C3 activity compared to controls.
- Heparin and Hep-NAc demonstrated inhibition of cobra venom factor-induced hemolysis.
- The modified heparin (Hep-NAc) showed inhibitory effects despite its reduced anticoagulant activity.
Conclusions:
- Commercial heparin and modified heparin (Hep-NAc) inhibit complement activation in vivo.
- This study validates the potential of heparin derivatives to regulate the complement system.
- Findings represent a step towards developing oligosaccharide-based drugs targeting complement activation.