Reduction by OK-432 of the monolayer contact-mediated inhibition of human natural killer cell activity.
In the present study we investigated the effect of OK-432, a streptococcus preparation, on the contact-mediated inhibition of human NK activity by primary cultures of monolayer cells. Either peripheral blood lymphocytes (PBL) or large granular lymphocytes (LGL) were incubated (2 x 10(6) cells/ml, total volume 2 ml) on confluent monolayer cells (uvea-derived fibroblasts, uvea-derived melanoma cells, or renal carcinoma cells) for 18 h in 24-well plates, washed twice, and tested for cytotoxicity against K562, a human myelogenous leukemia cell line, in a 4 h 51Cr-release assay. After contact with monolayer cells, NK activity of both PBL and LGL was significantly reduced. When these effector cells were preincubated with 0.1 U/ml of OK-432 for 18 h and then tested for the sensitivity to contact-mediated inhibition, the inhibition was significantly reduced. The pretreatment of monolayer cells with OK-432 or the addition of OK-432 into the coculture wells (of effector cells and monolayer cells) also significantly reduced the contact-mediated inhibition. Moreover, OK-432 (0.1 U/ml) reestablished the inhibited NK activity of PBL. These results suggest that OK-432 might enable NK cells to escape from the contact-mediated inhibition by monolayer cells and thus provide an additional potential mechanism for the observed clinical effectiveness of OK-432 reported by many groups.
Yagita
M
M
Department of Pathology, University of Helsinki, Finland.
Saksela
E
E
D000255:Adenosine Triphosphate / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000473:pathology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects*; D008545:Melanoma / Q000473:pathology; D010844:Picibanil / Q000494:pharmacology*; D013297:Streptococcus pyogenes; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014602:Uvea / Q000166:cytology; D014604:Uveal Neoplasms / Q000473:pathology
D007155:Immunologic Factors; D010844:Picibanil; D000255:Adenosine Triphosphate