Anti-microbial and lps-neutralizing synthetic peptides derived from human CAP 18

M. Hirataj, T. Kirikae, Y. Hirai, K. Yokota, N. Suuanuma, K. Oguma, R. F. Balinl, S. C. Wright, J. W. Larrick

Research output: Contribution to journalArticle

Abstract

We purified 18kDa cationic anti-microbial protein (CAP 18) with lipopolysaccharide (LPS)-neutralizing activities from rabbit granulocytes(Hirata et al. Inflmmun., 62. 1421-1426, 1994, Larricket aL J.lmmunoL, 152: 231-240, 1994)). We also cloned a CAP18 family protein from a human bone marrow library. The cloned DNA encxxtcd 140 amino acid residues (CAP181-140). Like the rabbit protein this molecule is comprised of two domains, a highly conserved N-terminal domain of unknown function and a less conserved C-terminal anti-microbial and LPS-neulralizing domain. In file present study, we synthesized new human peptides to identify, in more detail the active domain within C-terminal fragment. Synthetic peptide(27 mer; F12-V38) of C-tenuinal fragment binds to LPS, inhibits LPS-induced activation of Limulus amebocyte Ivsate. LPS-induced reactive nitrogen release by macrophages ',and protect nfice Iron1 LPS lethality. Treatment with the 27 mer peptide also blocked the increase in TNF-alpha levels induced by LPS injection. This peptide also showed antimicrobial activity versus both gram-negative bacteria such as Fcerichia coli O157:H7, Salmonella (vphimiurium, Klebsiella pneumoniae, Pseudomonas aeruginosa and gram-positive bacteria such as Staphylococcus aureus tt Streptococcus pneumoniae. Truncation of hydrophobic amino acids from this 27 mer peptide caused a significant decrease in all activities indicating that this 27-mer fragment is the minimal anti-microbial and LPSneutralizing domain of CAP18. The amphipathic and alpha-helical structure of this peptide may play a major role in the expression of these activities. The importance of C-terminus hydophobic residues in CAP 18 was also suggested. CAP 18 and derived peptides may act as host defense protein against infectious diseases, 'and have therapeutic potential for sepsis and endotodn shock.

Original languageEnglish
Pages (from-to)A1451
JournalFASEB Journal
Volume11
Issue number9
Publication statusPublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Hirataj, M., Kirikae, T., Hirai, Y., Yokota, K., Suuanuma, N., Oguma, K., Balinl, R. F., Wright, S. C., & Larrick, J. W. (1997). Anti-microbial and lps-neutralizing synthetic peptides derived from human CAP 18. FASEB Journal, 11(9), A1451.