Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis

E. L. Morgan, S. Sanderson, W. Scholz, D. J. Noonan, W. O. Weigle, T. E. Hugli

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Human C fragment C5a is known to be a proinflammatory mediator and more recently shown to be a potent modulator of both humoral and cell-mediated immunity. We recently reported that natural and recombinant C5a induces the synthesis of IL-6-specific mRNA and secreted protein from human monocytes. Our studies using analogue peptides that are homologous to the carboxyl- terminal sequence of human C5a, indicate that the 'effector' site for inducing IL-6 synthesis resides within the C-terminal region (C5a (70-74)) of the C5a molecule. C5a peptides containing the exact sequence of the natural factor were found to retain full agonist activity but exhibited low potency (0.01-0.1% of intact C5a). It was also shown that amino acid substitutions in the C5a peptides by aromatic/hydrophobic residues, outside the immediate effector site, resulted in analogue peptides with a substantial increase in potency relative to the most active natural peptide (C5a (56-74)). Moreover, these peptides approach the potency of natural C5a for induction of IL-6. Taken together, these results suggest that the inflammatory and immunoregulatory activities associated with C5a may, in part, be due to the synthesis of IL-6.

Original languageEnglish (US)
Pages (from-to)3937-3942
Number of pages6
JournalJournal of Immunology
Volume148
Issue number12
StatePublished - 1992

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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