Cytotoxicity and antigenicity of antimicrobial synthesized peptides derived from the beetle Allomyrina dichotoma defensin in mice.
Synthetic peptides, peptides A (Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)) and B (Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH(2)), derived from the beetle Allomyrina dichotoma defensin, have antimicrobial activities. Immunotoxicological effect of these peptides was evaluated by cytotoxicity of mouse peritoneal macrophages. In addition, antigenicity of these peptides was studied by evaluating antibody responses in mice immunized with these peptides. The toxicity of peptide A toward mouse peritoneal cells was less than that of polymyxin B, when morphologically evaluated in a cytotoxicity test. Almost all of mice injected intraperitoneally (i.p.) with either peptide A or B at 50-150 mg/kg survived, whereas all mice injected i.p. with polymyxin B at the doses of more than 25 mg/kg died within 24 h. Interestingly, almost all of mice injected intravenously with these peptides at the doses of 10 and 25 mg/kg also survived. Furthermore, mice immunized with these peptides conjugated with keyhole limpet hemocyanin (KLH) showed little or negligible anti-peptide A or B antibody production, although anti-KLH antibody was significantly produced. The results indicated that peptides A and B were less cytotoxic than polymyxin B and also had poor antigenicity to produce specific antibody in mice.
Koyama
Yukari
Y
National Institute of Animal Health, Tsukuba, Ibaraki, Japan.
Motobu
Maki
M
Hikosaka
Kenji
K
Yamada
Manabu
M
Nakamura
Kikuyasu
K
Saido-Sakanaka
Hisako
H
Asaoka
Ai
A
Yamakawa
Minoru
M
Isobe
Takashi
T
Shimura
Kameo
K
Kang
Chung-Boo
CB
Hayashidani
Hideki
H
Nakai
Yutaka
Y
Hirota
Yoshikazu
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D001517:Coleoptera; D023082:Defensins / Q000737:chemistry*; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007114:Immunization; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000276:immunology / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000906:Antibodies; D000941:Antigens; D023082:Defensins; D009842:Oligopeptides; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin