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Related Experiment Videos

Nickel and cobalt activate complement factor C3 faster than magnesium.

Fernando Acevedo1, Olof Vesterberg

  • 1Institute for Environmental Medicin, Karolinska Institute, Solna, Sweden. fernando.acevedo@imm.ki.se

Toxicology
|December 31, 2002
PubMed
Summary

Nickel (Ni2+) and cobalt (Co2+) ions accelerate complement factor C3 conversion to C3b, outperforming natural cofactor magnesium (Mg2+). This metal-induced complement activation may explain the immunotoxicity of nickel and cobalt.

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Area of Science:

  • Immunology
  • Biochemistry
  • Toxicology

Background:

  • The alternative complement pathway is crucial for innate immunity.
  • Magnesium (Mg2+) is the natural cofactor for complement factor C3 conversion.
  • The role of other divalent metal ions in complement activation is not fully understood.

Purpose of the Study:

  • To investigate the effect of nickel (Ni2+) and cobalt (Co2+) ions on complement factor C3 conversion.
  • To compare the stimulatory effects of Ni2+ and Co2+ with Mg2+.
  • To explore the potential immunotoxicity of Ni2+ and Co2+ through complement activation.

Main Methods:

  • Incubation of heparin plasma with various divalent metal ions.
  • Monitoring C3 to C3b conversion using light absorbance, isotachophoresis, immunofixation, and protein staining.

Related Experiment Videos

  • Assessing complement factor B (B) to Bb conversion via isotachophoresis and immunoblotting.

    • Main Results:

    • Ni2+ and Co2+ significantly accelerated C3 to C3b conversion, up to four times faster than Mg2+ at concentrations below 0.5 mM.
    • Optimal C3 conversion by Ni2+ or Co2+ occurred at 0.5 mM, with half of total C3 converted in 20 minutes at 37°C.
    • Increasing Ni2+ concentrations above 0.5 mM reduced the C3 conversion rate.
    • Activation of C3 by Ni2+, Co2+, and Mg2+ was accompanied by B to Bb conversion, while C4 remained unaffected.
    • Ca2+, Ba2+, Cu2+, and Zn2+ did not stimulate the complement cascade.

    Conclusions:

    • Ni2+ and Co2+ are potent stimulators of the alternative complement pathway, exceeding the activity of Mg2+.
    • The accelerated C3 fragment production induced by Ni2+ and Co2+ is a likely mechanism underlying their immunotoxicity.