0000000000304140
AUTHOR
H. U. Schorlemmer
Ability of the T cell-replacing polyanion dextran sulfate to trigger the alternate pathway of complement activation.
Dextran sulfate (DS) consumed C3 in C4 deficient guinea pig serum. This temperature-dependent reaction required Mg++ ions and could therefore be blocked by EDTA. Isolated C3 was not influenced by DS, but serum factors were required for C3 consumption. The C3 proactivator as well as C3 were converted to their activated state by DS in guinea pig and human serum, as revealed by immunoelectrophoretical analysis. DS generated anaphylatoxin activity in serum. It is concluded that DS activates C3 via the alternate pathway of complement activation. This potency of the polyanion might serve as a tentative explanation for its T cell-replacing effect in an antibody-forming system, which was reported b…
Autoreactivity to mouse C1q in a murine model of SLE.
A large proportion of systemic lupus erythematosus (SLE) patients develop glomerulonephritis, coincident with the appearance of autoantibodies to C1q, the Fc-recognizing collagen-like subcomponent of the first component of complement, C1. The MRL/lpr/lpr mouse is an established model for SLE, developing both antinuclear and anti-type II collagen autoantibodies, and rheumatoid factors(s), exhibiting reduced complement levels and later on developing glomerulonephritis and often arthritis. We report here an age-dependent decrease in serum C1q levels coincident with the development of IgG2b autoantibodies reactive with mouse C1q in MRL/lpr/lpr mice. Unlike IgG2b, although high levels of IgM, Ig…
Demonstration of High-Affinity Binding Sites for C3a Anaphylatoxin on Guinea-Pig Platelets
3H-serotonin release from guinea-pig platelets was demonstrated to be the consequence of C3a binding to these cells. A Scatchard analysis of dose-response data of the 125I-C3a binding pattern to guinea-pig platelets pointed to the existence of binding sites with high and low affinity for the C3a molecule (HA and LA receptors). HA receptors are specific for C3a with intact C-terminal arginine. whereas C3adesarg only interacts with LA receptors. The release of serotonin may be induced by a combined reaction of C3a with HA receptors and LA receptors on the platelet membrane.
Comparative study on biological effects of the guinea pig complement-peptide C3a and C3a-related synthetic oligopeptides
Dose-response experiments with guinea pig C3a and a synthetic hexapeptide (amino acid residues 72–77), representing the COOH-terminal sequence of human C3a, were performed in two recently described bioassay systems for C3a, i.e. cytotoxicity against tumor cells measured as LDH and 51Cr-release and non cytolytic serotonin release from guinea pig platelets. Compared to the classical anaphylatoxic assay (guinea pig ileum contraction), nearly identical reactivities were observed in all three test systems with C3a and, although quantitatively different, with hexapeptide.