Superoxide production by phagocytes in myeloid Graffi tumor-bearing hamsters.

A progressive suppression of the phagocytic ability of peritoneal macrophages and polymorphonuclears (PMNs) in hamsters with transplanted myeloid tumors was previously established. The i.p. application of Cu/Zn SOD, isolated from the fungal strain Humicola lutea (HLSOD) (2 injections before and 5 injections after tumor transplantation) induced the mean survival time of the animals as well as a temporally stimulating action on the macrophage and PMNs phagocyting indices. In the present work, the superoxide production of peritoneal macrophages and PMNs during 30 days of tumor progression was followed. Effects of the application of HLSOD in an optimal protective dose on the superoxide production in peritoneal macrophages and blood PMNs were examined. The spontaneous and phorbol-myristate acetate (PMA)-inducible O2- production in both types of phagocytes was 4-5-fold increased in tumor-bearing hamsters (TBH), as compared to the controls, at day 14 after tumor transplantation (the day of tumor appearance in transplanted animals). Furthermore, O2- production was also similar to the control values for the following days of observation. HLSOD treatment of TBH induced a normalization of superoxide production in macrophages and PMNs. Therefore, the established decrease of superoxide anions in phagocyting cells of TBH indicates possible effects of HLSOD on the host antioxidant defense.

Treatment of adjuvant arthritis in mice with yeast superoxide dismutase.

Yeast Cu/Zn superoxide dismutase (SODy) was used for treatment of adjuvant-induced arthritis in mice. SODy was applied intraperitoneally (i.p.) in doses of 10 mg/kg (30,000 U/kg) and 30 mg/kg (90,000 U/kg) one or three times daily on consecutive days. It was very effective in reducing the paw swelling whether administered before or immediately after induction or when the treatment began at the onset of inflammation or at the peak of the arthritic process. The effect of yeast SOD was compared to that of commercial SOD from bovine erythrocytes (SODb), as well as with indomethacin treatment. Histological data confirmed the antiinflammatory effect of yeast SOD. The schedules and doses tested did not elicit anti-SOD antibodies in serum.

Effect of Escherichia coli L-form cytoplasmic membranes on the interaction between macrophages and Lewis lung carcinoma cells: scanning electron microscopy.

Scanning electron microscopy (SEM) investigations on the interactions between peritoneal macrophages from Lewis lung carcinoma (LLC)-bearing mice and LLC tumour cells during 21 days after tumour implantation were carried out. The action of lipopolysaccharide (LPS)-containing cytoplasmic membranes (CM), from the stable protoplast type L-form of Escherichia coli, on the activity of in vitro phagocytosis was studied; CM induced a continuous increase in macrophage numbers. Activation of macrophage surfaces in healthy and tumour-bearing mice was established. Lamelipods, pseudopods and migration fringes 14 days after CM application were seen. Crater-like cavities deeply in the macrophage cells as well as adherent or prominent engulfed tumour cells within macrophages were observed during in vitro interaction with LLC cells. Macrophages from tumour-bearing mice without CM treatment showed less activation evaluated by SEM during earlier stages of tumour growth. The SEM investigation proved the temporary stimulating effect of E. coli L-form CM on the cell surface activation of peritoneal macrophages in healthy and LLC-bearing mice.

Effect of a total extract from Fraxinus ornus stem bark and esculin on zymosan- and carrageenan-induced paw oedema in mice.

This study investigates the total ethanol extract (TE) of the stem bark of Fraxinus ornus and its constituent esculin (EN). They inhibited classical pathway (CP) and alternative pathway (AP) of complement activation in mouse serum. After intraperitoneal administration the total extract displayed antiinflammatory activity in both zymosan- and carrageenan-induced paw oedema in mice. The results suggest that the traditional use of Fraxinus ornus stem bark extracts in the treatment of inflammatory disorders is at least partially due to its coumarin constituents.

Antiinflammatory effect of superoxide dismutase (SOD). Comparison between yeast and bovine SOD on some complement-mediated reactions in vitro and in vivo.

The effect of CulZn superoxide dismutases from yeast cells (SODy) and commercial SOD from bovine erythrocytes (SODb) on zymosan-induced inflammation in mice and on complement activity in normal human serum (NHS) was studied. Zymosan-induced oedema formation was moderately suppressed by SODb. The alternative pathway (AP) activity in mouse serum was strongly inhibited after i.p. treatment with SODy. Comparison between the two enzymes showed different mode of action on the classical pathway (CP) as compared to the AP of complement activation. The inhibitory effect caused by SODy was more pronounced and strongly time- and temperature-dependent. SODy affected several activation steps in the complement cascade, while the inhibition caused by SODb was mainly directed to C1 of the complement activity. The powerful action of SODy on AP activity may be attributed to the oligosaccharide moiety in the enzyme molecule from yeast origin.