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.
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.
Andersson
M
M
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Gunne
H
H
Agerberth
B
B
Boman
A
A
Bergman
T
T
Sillard
R
R
Jörnvall
H
H
Mutt
V
V
Olsson
B
B
Wigzell
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D001483:Base Sequence; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology; D007421:Intestine, Small / Q000737:chemistry; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011510:Proteolipids / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D018076:DNA, Complementary; D007376:Interleukin-2; C093238:NK-lysin; D011510:Proteolipids; D011663:Pulmonary Surfactants