Complement activation pathways in murine immune complex-induced arthritis and in C3a and C5a generation in vitro

Clin Exp Immunol. 2010 Jan;159(1):100-8. doi: 10.1111/j.1365-2249.2009.04035.x. Epub 2009 Oct 19.


The alternative pathway (AP) of complement alone is capable of mediating immune complex-induced arthritis in the collagen antibody-induced arthritis (CAIA) model in mice. Whether the classical pathway (CP) or lectin pathway (LP) alone can mediate CAIA is not known. Using mice genetically deficient in different complement components, our results reported herein establish that the CP and LP alone are each incapable of mediating CAIA. A lower level or absence of C3 and/or C5 activation by the CP may be possible explanations for the importance of the AP in CAIA and in many murine models of disease. In addition, other investigators have reported that CP C5 convertase activity is absent in mouse sera. To address these questions, we employed an in vitro system of adherent immunoglobulin (Ig)G-induced complement activation using plates coated with murine anti-collagen monoclonal antibody (mAb). These experiments used complement-deficient mouse sera and wild-type mouse or normal human sera under conditions inactivating either the CP (Ca(++) deficiency) or the AP (mAb inhibitory to factor B). Robust generation of both C3a and C5a by either the AP or CP alone were observed with both mouse and human sera, although there were some small differences between the species of sera. We conclude that neither the CP nor LP alone is capable of mediating CAIA in vivo and that mouse sera exhibits a high level of IgG-induced C5a generation in vitro through either the CP or AP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Collagen Type II / immunology
  • Complement C1q / genetics
  • Complement C1q / metabolism
  • Complement C3 / genetics
  • Complement C3 / metabolism
  • Complement C3a / metabolism*
  • Complement C4 / metabolism
  • Complement C5a / metabolism*
  • Complement Factor B / genetics
  • Complement Factor B / immunology
  • Complement Factor B / metabolism
  • Complement Factor D / genetics
  • Complement Factor D / metabolism
  • Complement Pathway, Alternative / immunology*
  • Complement Pathway, Classical / immunology*
  • Complement Pathway, Mannose-Binding Lectin / immunology*
  • Complement System Proteins / genetics
  • Complement System Proteins / metabolism
  • Female
  • Foot / pathology
  • Humans
  • Immunoglobulin G / immunology
  • Joints / metabolism
  • Joints / pathology
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Serum / immunology
  • Serum / metabolism


  • Antibodies, Monoclonal
  • Collagen Type II
  • Complement C3
  • Complement C4
  • Immunoglobulin G
  • Lipopolysaccharides
  • Complement C1q
  • Complement C3a
  • Complement C5a
  • Complement System Proteins
  • Complement Factor D
  • Complement Factor B