ABSTRACT
The natural killer (NK) cell activity of peripheral blood mononuclear cells (PBMC) from healthy human volunteers was studied following in vitro incubation with ImuVert, a biological response modifier derived from the bacterium Serratia marcescens. Exposure of these cells to ImuVert for as little as 10 minutes followed by an additional incubation in vitro of at least 12 hours and optimally 18 hours resulted in a substantial, consistent, and dose-dependent augmentation of NK cell activity against K562 tumor cells. Additional studies indicate that the augmented cell expressed the leu 11 cell surface marker and that peripheral blood monocytes were essential in the induction of augmented NK cell activity but were not the effector cell of NK activity.
Subject(s)
Adjuvants, Immunologic/pharmacology , Immunologic Factors/pharmacology , Killer Cells, Natural/immunology , Adjuvants, Immunologic/isolation & purification , Adult , Antibodies, Monoclonal , Biological Products , Cytotoxicity, Immunologic , Female , Humans , In Vitro Techniques , Killer Cells, Natural/drug effects , Male , Polymyxin B/pharmacology , Serratia marcescens/analysis , Tumor Cells, Cultured/drug effectsABSTRACT
We previously reported that natural killer cell activity of peripheral blood mononuclear cells (PBMC) from healthy human subjects was augmented following in vitro incubation in ImuVert, a biologic response modifier derived from the bacterium Serratia marcescens. In the current investigation, we found that exposure of PBMC to ImuVert, 3-40 micrograms/ml, for 18 hr, resulted in significant and dose-dependent augmentation of three other types of cell-mediated cytotoxicity: K cell-mediated antibody-dependent cellular cytotoxicity (ADCC), monocyte-mediated ADCC, and cytotoxic T-cell activity against allogeneic PBMC. These and previous findings suggest that ImuVert may have a broad range of stimulatory effects on immune function.
Subject(s)
Antibody-Dependent Cell Cytotoxicity , Immunologic Factors/pharmacology , T-Lymphocytes, Cytotoxic/immunology , Adult , Biological Products , Cytotoxicity, Immunologic , Dose-Response Relationship, Immunologic , Humans , Immunologic Factors/administration & dosage , In Vitro Techniques , Killer Cells, Natural/immunology , Middle Aged , Monocytes/immunologyABSTRACT
The ability of polyribosomes, obtained from several bacterial species, to suppress the development of cutaneous SaD2 fibrosarcomas in DBA/2 mice were evaluated. Suppression of tumor appearance depended upon the tumor load at the time of treatment, dose of polyribosomes, and species source of polyribosomes, with Serratia marcescens being superior to Escherichia coli, Streptococcus pneumoniae, Mycobacterium bovis (Pasteur), Mycobacterium smegmatis, and Propionibacterium acnes (formerly Corynebacterium parvum). A single injection of 5 or 50 microgram of Serratia polyribosomes at the tumor site 72 hr after the intradermal administration of 1.5 X 10(3) SaD2 cells resulted in 66 to 95% survival. All untreated animals expired within 50 days. Tumor suppression occurred at both flank and footpad sites. Presensitization with polyribosomes and incorporation of polyribosomes into adjuvant were not required for the tumor-suppressive effect. Treatment of Serratia polyribosomes with RNase or pronase reduced the number of survivors. Endotoxin was not detectable with the Limulus amebocyte lysate assay.
