caa a22 4500 469073810 CHVBK 20180323132929.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF01789335 doi (NATIONALLICENCE)springer-10.1007/BF01789335 Effect of picibanil (OK432) on neutrophil-mediated antitumor activity: Implication of monocyte-derived neutrophil-activating factors [Elektronische Daten] [Kuender Yang, Richard Stone, Chung-Shinn Lee, Tsu-Yi Chao, Shin-Nan Cheng, Men-Fang Shaio] Summary: Picibanil (OK432), an extract from streptococci, has been widely utilized to treat malignant ascites and pleural effusions. The antitumor mechanism is believed to include complement-mediated neutrophil activation. Employing a flow-cytometric analysis of actin polymerization as an indicator of cell activation as well as a tumor proliferation assay, we have found that monocytederived neutrophil-activating factors were involved in OK432-induced neutrophil activation as well as antitumor activity. OK432-stimulated (0.1 KE/ml; 0.01 mg/ml) monocyte supernatants (OKMS) induced neutrophil actin polymerization and chemotaxis. OKMS were responsible for neutrophil-mediated inhibition of human leukemic (CEM) cell proliferation and stimulated neutrophils to produce superoxide in the presence of CEM leukemic cells at an effector/target ratio higher than 20/1. In contrast, OK432 alone, OK432-stimulated lymphocyte supernatants, or OK432-stimulated neutrophil supernatants had no effect on neutrophil activation or suppression of tumor cell proliferation. OK432 in combination with mononuclear cells also had no effect on the inhibition of CEM cell proliferation. Pretreatment of OKMS at 56°C for 30 min did not affect its ability to activate neutrophils, implying that complement activation is not responsible for the neutrophil activation. Supernatants from OK432-stimulated mononuclear cells, as determined by enzyme-linked immunosorbent assays and radioimmunoassays, contained high levels of interleukin-8 (IL-8; 1567±145 pg/ml) and tumor necrosis factor (TNFα; 2105±152 pg/ml), low levels of leukotriene B4 (800±45 pg/ml) and IL-1β (180±22 pg/ml), but interferon γ was not detectable. IL-1β, IL-8, and TNFα transcripts, undetectable in untreated monocytes, increased significantly after 30-60 min exposure to OK432. These results suggest that neutrophil-activating factors from monocytes or resident macrophages may play an important role in the OK432-induced neutrophil activation and antitumor activity. Springer-Verlag, 1992 OK432 nationallicence Neutrophil nationallicence Antitumor activity nationallicence Yang Kuender Department of Pediatrics, National Defense Medical Center, Taiwan, R. O. C. aut Stone Richard Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA aut Lee Chung-Shinn Department of Parasitology and Tropical Medicine, National Defense Medical Center, Taiwan, R. O. C. aut Chao Tsu-Yi Department of Medicine, National Defense Medical Center, Taiwan, R. O. C. aut Cheng Shin-Nan Department of Pediatrics, National Defense Medical Center, Taiwan, R. O. C. aut Shaio Men-Fang Department of Parasitology and Tropical Medicine, National Defense Medical Center, Taiwan, R. O. C. aut Cancer Immunology, Immunotherapy Springer-Verlag 35/4(1992-07-01), 277-282 0340-7004 35:4<277 1992 35 262 https://doi.org/10.1007/BF01789335 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01789335 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yang Kuender Department of Pediatrics, National Defense Medical Center, Taiwan, R. O. C aut NATIONALLICENCE 700 1- Stone Richard Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA aut NATIONALLICENCE 700 1- Lee Chung-Shinn Department of Parasitology and Tropical Medicine, National Defense Medical Center, Taiwan, R. O. C aut NATIONALLICENCE 700 1- Chao Tsu-Yi Department of Medicine, National Defense Medical Center, Taiwan, R. O. C aut NATIONALLICENCE 700 1- Cheng Shin-Nan Department of Pediatrics, National Defense Medical Center, Taiwan, R. O. C aut NATIONALLICENCE 700 1- Shaio Men-Fang Department of Parasitology and Tropical Medicine, National Defense Medical Center, Taiwan, R. O. C aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 35/4(1992-07-01), 277-282 0340-7004 35:4<277 1992 35 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer