NK-lysin, a Novel Effector Peptide of Cytotoxic T and NK Cells. Structure and cDNA Cloning of the Porcine Form, Induction by Interleukin 2, Antibacterial and Antitumour Activity

EMBO J. 1995 Apr 18;14(8):1615-25.

Abstract

A 78 residue antimicrobial, basic peptide, NK-lysin, with three intrachain disulfide bonds was purified from pig small intestine and characterized. A corresponding clone was isolated from a porcine bone marrow cDNA library. The 780 bp DNA sequence had a reading frame of 129 amino acids which corresponded to NK-lysin. The clone was used to show that stimulation with human interleukin-2 induced synthesis of NK-lysin-specific mRNA in a lymphocyte fraction enriched for T and NK cells. Lower levels of mRNA were detected in tissues known to contain T and NK cells, such as small intestine, spleen and colon. Interleukin-2 also induced both proliferation of the lymphocyte fraction and cytolytic function in these cells. Immunostaining showed that NK-lysin was present in cells positive for CD8, CD2 and CD4. NK-lysin showed high anti-bacterial activity against Escherichia coli and Bacillus megaterium and moderate activity against Acinetobacter calcoaceticus and Streptococcus pyogenes. The peptide showed a marked lytic activity against an NK-sensitive mouse tumour cell line, YAC-1, but it did not lyse red blood cells. The amino acid sequence of NK-lysin exhibits 33% identity with a putative human preproprotein, NKG5, of unknown function but derived from a cDNA clone of activated NK cells. We suggest that NK-lysin is a new effector molecule of cytotoxic T and NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Infective Agents / metabolism*
  • Anti-Infective Agents / pharmacology
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology
  • Base Sequence
  • Bone Marrow / physiology
  • Bone Marrow Cells
  • Cloning, Molecular
  • Cytotoxicity, Immunologic
  • DNA, Complementary / genetics
  • Fluorescent Antibody Technique
  • Gene Expression / drug effects
  • Interleukin-2 / pharmacology
  • Intestine, Small / chemistry
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Proteolipids / genetics
  • Proteolipids / immunology
  • Proteolipids / metabolism*
  • Proteolipids / pharmacology
  • Pulmonary Surfactants / genetics
  • Pulmonary Surfactants / immunology
  • Pulmonary Surfactants / metabolism*
  • Pulmonary Surfactants / pharmacology
  • Sequence Homology, Amino Acid
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Tumor Cells, Cultured

Substances

  • Anti-Infective Agents
  • Antineoplastic Agents
  • DNA, Complementary
  • Interleukin-2
  • NK-lysin
  • Proteolipids
  • Pulmonary Surfactants

Associated data

  • GENBANK/X85431