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IgG and complement-mediated tissue damage in the absence of C2: evidence of a functionally active C2-bypass pathway in a guinea pig model.

Publication ,  Journal Article
Wagner, E; Platt, JL; Howell, DN; Marsh, HC; Frank, MM
Published in: J Immunol
September 15, 1999

In vitro complement-mediated lysis of heavily sensitized sheep erythrocytes by C4-deficient (C4D) guinea pig and C2-deficient (C2D) human sera was demonstrated some years ago. It was postulated that these "complement-bypass" pathways resulted from activation of C1 and components of the alternative pathway. We used normal, C2D, and C4D guinea pigs in a Forssman shock model to test the in vivo relevance of the C2- and C4-bypass pathways of complement activation. High concentrations of both anti-Forssman Ab and C2D or C4D guinea pig serum induced efficient lysis of sheep erythrocytes in vitro. The most efficient lysis was observed when IgG Ab and C2D guinea pig serum were used. Blocking either the classical pathway (treatments with EGTA-Mg2+ or soluble recombinant complement receptor type 1 (sCR1)) or the alternative pathway (treatment with heating at 50 degrees C, sCR1, or soluble recombinant CR1 lacking the first of the four long homologous repeat sequences (sCR1[desLHR-A])) inhibited lysis; both pathways were required for lysis of sheep erythrocytes by C2D and C4D guinea pig sera. i.v. injection of anti-Forssman Ab in normal guinea pigs resulted in rapid death from pulmonary shock, whereas C4D guinea pigs had no adverse effect. Surprisingly, C2D guinea pigs either died in a delayed fashion or had a sublethal reaction. sCR1 treatment prevented Forssman shock in both normal and C2D guinea pigs, whereas sCR1[desLHR-A] prevented Forssman shock only in C2D animals. Our results suggest that the C2-bypass pathway occurs in vivo to produce tissue damage. Activation of complement in the absence of C2 appears to be far more efficient than in the absence of C4.

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

September 15, 1999

Volume

163

Issue

6

Start / End Page

3549 / 3558

Location

United States

Related Subject Headings

  • Pulmonary Edema
  • Models, Immunological
  • Lung
  • Injections, Intravenous
  • Immunology
  • Immunoglobulin G
  • Humans
  • Hemolysis
  • Guinea Pigs
  • Complement Pathway, Classical
 

Citation

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Wagner, E., Platt, J. L., Howell, D. N., Marsh, H. C., & Frank, M. M. (1999). IgG and complement-mediated tissue damage in the absence of C2: evidence of a functionally active C2-bypass pathway in a guinea pig model. J Immunol, 163(6), 3549–3558.
Wagner, E., J. L. Platt, D. N. Howell, H. C. Marsh, and M. M. Frank. “IgG and complement-mediated tissue damage in the absence of C2: evidence of a functionally active C2-bypass pathway in a guinea pig model.J Immunol 163, no. 6 (September 15, 1999): 3549–58.
Wagner E, Platt JL, Howell DN, Marsh HC, Frank MM. IgG and complement-mediated tissue damage in the absence of C2: evidence of a functionally active C2-bypass pathway in a guinea pig model. J Immunol. 1999 Sep 15;163(6):3549–58.
Wagner E, Platt JL, Howell DN, Marsh HC, Frank MM. IgG and complement-mediated tissue damage in the absence of C2: evidence of a functionally active C2-bypass pathway in a guinea pig model. J Immunol. 1999 Sep 15;163(6):3549–3558.

Published In

J Immunol

ISSN

0022-1767

Publication Date

September 15, 1999

Volume

163

Issue

6

Start / End Page

3549 / 3558

Location

United States

Related Subject Headings

  • Pulmonary Edema
  • Models, Immunological
  • Lung
  • Injections, Intravenous
  • Immunology
  • Immunoglobulin G
  • Humans
  • Hemolysis
  • Guinea Pigs
  • Complement Pathway, Classical