Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions

Abstract

Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected. Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines. A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice, yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca fractions and monokines might be mediated by activated peritoneal macrophages.

Nocardia fractions, NLD and NWSM, induce tumor necrosis factor‐α secretion in human monocytes: Role of protein kinase C

“…Indeed, NWSM was less mitogenic than NLD for B lymphocytes [l]. In contrast, NWSM was more potent than NDCM, a less purified fraction of Nocurdia, in reducing lung invasion in tumor-grafted mice [3]. NWSM had the most pronounced promoting effect on splenic NK activity, whereas peptidoglycan derivatives, the other molecule family extracted from Nocardia, induced a cytotoxic activity only in peritoneal cells [5].…”

“…opuca share, with some bacterial preparations, the ability to activate macrophages [6, 71. Indeed, in vivo treatment with Nocardia preparations primed murine peritoneal macrophages to produce hydrogen peroxide in response to phorbol myristate acetate (PMA) or zymosan particles [3]. Murine peritoneal macrophages stimulated by Nocardia extracts released substances which stimulated thymocyte proliferation and exhibited strong homology with IL-1 [8].…”

A pharmacokinetic study of JOMO-tech® in rats

“…The marked immunostimulatory effect of cell wall fractions from Nocardia opaca has been intensively investigated (1)(2)(3)(4)(5)(6). JOMO-tcch® is a product based on an extract from N. opaca cell walls, and which mainly contains oligopeptides and small amounts of polysaccharides.…”

Macrophage nitric oxide synthase (NOS) activation by Nocardia opaca fractions and 15- and 56-kD isolated antigens

“…Isolated fractions of Nocardia were shown to exert adjuvant effect [2], to induce regression of experimental tumours [3][4][5][6][7], to enhance protection against irradiation [8,9], and to promote resistance to infections [10]. These activities include activation of natural killer (NK) cells and macrophages, followed by enhanced cytotoxicity of these cells and production of tumour necrosis factor-alpha (TNF-), IL-1 and other cytokines [3,[11][12][13][14][15][16][17] and stimulation of B cells to proliferation and differentiation into immunoglobulin-secreting cells [1,2,10,18,19].…”

“…are produced by an inducible isoform of NO synthase (iNOS) in many activated cells where the iNOS gene is transcriptionally active. In mouse peritoneal macrophages expression of iNOS results from treatment with interferongamma (IFN-) alone or IFN-together with bacterial lipopolysaccharide (LPS); it is suppressible at transcriptional, translational and post-translational level by polyamines, iron (Fe 3 ), cytokines (interleukins: IL-4, IL-8, IL-10, transforming growth factorbeta (TGF-), platelet-derived growth factor (PDGF)), and other substances [23][24][25].…”