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

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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 - Jan 1 1992

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Interleukin-6
Peptides
Amino Acid Substitution
Cellular Immunity
Monocytes
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Morgan, E. L., Sanderson, S., Scholz, W., Noonan, D. J., Weigle, W. O., & Hugli, T. E. (1992). Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis. Journal of Immunology, 148(12), 3937-3942.

Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis. / Morgan, E. L.; Sanderson, S.; Scholz, W.; Noonan, D. J.; Weigle, W. O.; Hugli, T. E.

In: Journal of Immunology, Vol. 148, No. 12, 01.01.1992, p. 3937-3942.

Research output: Contribution to journalArticle

Morgan, EL, Sanderson, S, Scholz, W, Noonan, DJ, Weigle, WO & Hugli, TE 1992, 'Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis', Journal of Immunology, vol. 148, no. 12, pp. 3937-3942.
Morgan EL, Sanderson S, Scholz W, Noonan DJ, Weigle WO, Hugli TE. Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis. Journal of Immunology. 1992 Jan 1;148(12):3937-3942.
Morgan, E. L. ; Sanderson, S. ; Scholz, W. ; Noonan, D. J. ; Weigle, W. O. ; Hugli, T. E. / Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis. In: Journal of Immunology. 1992 ; Vol. 148, No. 12. pp. 3937-3942.
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