In vitro effects of an acyltripeptide, FK565, on antitumor effector activities and on metabolic activities of human monocytes and granulocytes.
In vitro effects of an immunostimulatory acyltripeptide, FK565, on antitumor and metabolic activities of human leukocytes were studied. Monocyte cytotoxicity against A375 melanoma targets was significantly increased following pretreatment with FK565 at concentrations of 1 microgram/ml or more. The tripeptide also up-regulated anti-tumor cytostasis by monocytes and showed a strong stimulatory effect on superoxide generation by resting monocytes over a wide range of FK565 concentrations after 18 h preincubation. The monocyte preparations contained an average of 76% LeuM3+HLA-DR+, 12% LeuM3+HLA-DR- and 10% LeuM3-HLA-DR+ cells, and this phenotype distribution was not altered after incubation with FK565. At concentrations above 1 microgram/ml and after 2 h preincubation, FK565 also increased superoxide generation by resting but not stimulated granulocytes. Pre-exposure of cultured bovine endothelial cells to the peptide resulted in a significant inhibition of fMLP-stimulated granulocyte adherence to these cells. These data indicate that in vitro incubation of human monocytes and granulocytes with FK565 (0.1-100 micrograms/ml) had resulted in simultaneous up-regulation of several anti-tumor functions mediated by these cells.
Wang
Y L
YL
Department of Pathology, University of Pittsburgh School of Medicine, PA.
Kaplan
S
S
Whiteside
T
T
Herberman
R B
RB
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000954:Antigens, Surface / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009369:Neoplasms / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D009842:Oligopeptides / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D009842:Oligopeptides; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine; D013755:Tetradecanoylphorbol Acetate