Recombinant soluble human complement receptor type 1 inhibits inflammation in the reversed passive arthus reaction in rats

J Immunol. 1991 Jan 1;146(1):250-6.

Abstract

The human CR1 was genetically engineered by site directed mutagenesis into a truncated form which was secreted from transfected Chinese hamster ovary cells. This soluble recombinant CR1 (sCR1) was purified from the supernatants of the Chinese hamster ovary cells cultured in a hollow fiber bioreactor. sCR1 inhibits the C3 and C5 convertases of the classical and the alternative pathways in vitro. The ability of sCR1 to inhibit the immune complex-mediated inflammation in vivo was tested in a rat reversed passive Arthus reaction model. Administration of sCR1 at the dermal sites reduced the Arthus vasculitis in a dose-dependent manner as judged by both gross and microscopic examination, as well as by immunohistologic localization of C3 and C5b-9 neoantigen deposits. These data suggest that sCR1 inhibits the Arthus reaction by interrupting the activation of the C cascade, hence limiting the detrimental immune complex-induced tissue damage in vivo.

MeSH terms

  • Animals
  • Arthus Reaction / immunology*
  • Arthus Reaction / pathology
  • Complement Activation
  • Complement System Proteins / metabolism*
  • Fluorescent Antibody Technique
  • Humans
  • Immunization, Passive
  • Molecular Weight
  • Rats
  • Rats, Inbred Strains
  • Receptors, Complement / chemistry
  • Receptors, Complement / genetics
  • Receptors, Complement / physiology*
  • Receptors, Complement 3b
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Skin / immunology
  • Skin / pathology
  • Solubility
  • Transfection

Substances

  • Receptors, Complement
  • Receptors, Complement 3b
  • Recombinant Proteins
  • Complement System Proteins