Acidic polyamino acids inhibit human eosinophil granule major basic protein toxicity: Evidence of a functional role for ProMBP

Robert L. Barker, Robert H. Gundel, Gerald J. Gleich, James L. Checkel, David A. Loegering, Larry R. Pease, Kimm J. Hamann

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Eosinophil granule major basic protein (MBP), a potent toxin for helminths and mammalian cells in vitro, is a single poly peptide chain rich in arginine. MBP has been localized on damaged helminths and tissues in hypersensitivity diseases including bronchial asthma. The MBP cDNA indicates that MBP is translated as a slightly acidic preproprotein with an acidic propart. To test the hypothesis that the acidic pro-part of proMBP inhibits the toxicity of mature MBP, acidic polyamino acids (aa) were used as antagonists of MBP toxicity to K562 cells and guinea pig tracheal epithelium and used as antagonists of MBP airway hyperresponsiveness in primates. The acidic poly aa inhibited MBP toxicity and MBP airway hyperresponsiveness. The acidic poly aa inhibited MBP toxicity in a charge-dependent manner similar to that proposed for proMBP, suggesting that the acidic pro-part of proMBP functions to mask mature MBP toxicity. This inhibition was not limited to MBP, but also applied to polyarginine and eosinophil cationic protein. These acidic poly aa may be useful to inhibit the actions of a number of cationic toxins released by the eosinophil in numerous hypersensitivity diseases.

Original languageEnglish (US)
Pages (from-to)798-805
Number of pages8
JournalJournal of Clinical Investigation
Volume88
Issue number3
DOIs
StatePublished - Sep 1991

Keywords

  • Airway hyperresponsiveness
  • Anionic polymers
  • Bronchial asthma
  • Eosinophil cationic protein
  • Polyarginine

ASJC Scopus subject areas

  • Medicine(all)

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