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Related Experiment Videos

Complement activation in factor D-deficient mice.

Y Xu1, M Ma, G C Ippolito

  • 1Department of Medicine, University of Alabama, Birmingham, AL 35294, USA. rheu019@uabdpo.dpo.uab.edu

Proceedings of the National Academy of Sciences of the United States of America
|November 29, 2001
PubMed
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Factor D deficiency impairs alternative complement pathway activation, impacting bacterial defense but not energy balance. This study reveals factor D is not essential for cobra venom factor-induced C3 cleavage.

Area of Science:

  • Immunology
  • Complement System Biology

Background:

  • The alternative complement pathway is crucial for innate immunity and host defense.
  • Its role in systemic energy balance remains largely unexplored.
  • Factor D is a key enzyme in the alternative pathway cascade.

Purpose of the Study:

  • To investigate the role of factor D in complement activation and host defense.
  • To explore the potential involvement of the alternative pathway in regulating systemic energy balance.
  • To generate and characterize factor D-deficient mice for in vivo studies.

Main Methods:

  • Gene targeting was used to create factor D-deficient mice.
  • Complement activation was assessed using alternative pathway activators like rabbit erythrocytes and zymosan.

Related Experiment Videos

  • Cobra venom factor (CVF) was injected to study C3 and factor B activation.
  • In vitro studies examined C3 and factor B cleavage kinetics in deficient serum.
  • Main Results:

    • Factor D-deficient mice showed normal development and body weight.
    • Alternative pathway activators failed to initiate complement activation in deficient serum.
    • CVF induced significant C3 reduction in factor D-deficient mice, unlike in factor B-deficient mice.
    • CVF-dependent C3 cleavage in deficient serum required Mg(2+) and did not involve factor B cleavage.
    • Opsonization of Streptococcus pneumoniae was significantly slower in factor D-deficient serum.

    Conclusions:

    • Proteolytic cleavage of factor B by factor D is not essential for CVF-mediated C3 cleavage.
    • The alternative complement pathway significantly contributes to early antibacterial host defense.
    • Factor D deficiency does not appear to affect systemic energy balance regulation.