Pasquale Mastroeni

Biology of salmonella

Proceedings of a NATO Advanced Research Workshop held at Portorosa, Italy in May 1992. This volume presents the invited lectures and extended summaries of the contributed papers. Reports from the epidemiologists emphasize the continuing extent of salmonellosis worldwide, the increasing problem of dr

Different effects of bacterial lipopolysaccharide on superoxide anion production by macrophages from normal and tumor-bearing rats

Bacterial endotoxins or lipopolysaccharides (LPS) exhibit a wide range of modulatory activities on immunocompetent cells. Among the numerous effects of LPS on macrophages, an enhancement of superoxide anion (O2-) release has been reported. In previous studies carried out on tumor-bearing rats, it was found that several functions of peritoneal macrophages such as phagocytic, microbicidal and antiviral activities were depressed. In this paper we evaluated the spontaneous or phorbol myristate acetate (PMA)-induced production of superoxide anion by macrophages from tumor-bearing rats with respect to controls. Moreover, the effect of in vitro priming with LPS on O2- production by the same cells was studied. It was found that the pattern of superoxide release by macrophages from tumor-bearing rats is significantly different from controls. Preincubation of macrophages from normal rats with LPS enhanced the spontaneous and PMA-induced production of O2-. In contrast, the same concentrations of LPS did not prime macrophages from tumor-bearing rats.

Immunity Mechanisms in Experimental Salmonellosis

Salmonellae are generally believed to be facultative intracellular parasites capable of growing inside professional phagocytes, although this view has been questioned (Hsu, this volume). Some salmonellae have a broad host range and can affect many species (“salmonellae of animal origin”), whereas others are more restricted and cause disease in only one or a few hosts, such as S. typhi, the agent of human typhoid fever, which affects only humans. The latter tend to cause invasive disease (e.g. enteric fever), whereas human infections with “animal” salmonellae — which can be invasive in animals — can be localised to the gut (salmonella gastroenteritis).

The restoration of impaired macrophage functions using as immunomodulator the Corynebacterium granulosum-derived P40 fraction

Many microorganisms and compounds of microbial origin exhibit immunomodulatory activities and have been extensively used in immunotherapy of experimental animal tumors and in patients with neoplasia. In this paper we describe the effect of the C. granulosum-derived P40 fraction on the growth and metastatization of the transplantable epithelioma T8 of Guèrin. Moreover, we evaluated the effect of P40 treatment on several depressed macrophage functions of tumor-bearing rats. In particular, the phagocytic and chemotactic activities of such cells were studied, as well as the antiviral intrinsic and extrinsic activities against HSV-1 and the anti-Toxoplasma gondii activity. All these functions were depressed in untreated tumor-bearing rats. Administration of a single intravenous injection of P40 fraction led to the restoration of all depressed macrophage activities to normal values. In particular, the possibility of restoring the antimicrobial activity of macrophages from tumor-bearing rats by treatment with this immunomodulator is of great concern when one considers the increasing incidence of opportunistic infections in immunocompromised hosts. Results are discussed in terms of both the possible mechanism of action of P40 and of its possible target cells.

Inhibition of normal rat macrophage functions by soluble tumor products

SummaryThe phagocytic and chemotactic activities of normal rat peritoneal macrophages were inhibited by sera from tumor-bearing rats (TBR) and 3 M KCl extracts of tumor mass. However, sera from Corynebacterium parvum- or Listeria monocytogenes-treated TBR did not inhibit phagocytosis. On the other hand, sera from C. parvum-treated, but not from L. monocytogenes-treated TBR still inhibited the chemotactic response of the normal macrophages. Furthermore, 3 M KCl extracts of tumors from C. parvum-treated TBR did not inhibit phagocytosis and chemotactic response of the same cells. Similar results were obtained with extracts of tumor masses from L. monocytogenes-treated rats. It is suggested that treatment with bacterial immunomodulators can influence the release from neoplastic cells of soluble products influencing normal macrophage functions.

EVALUATION OF MACROPHAGE ANTIVIRAL ACTIVITY IN PATIENTS AFFECTED BY NEOPLASIA

The intrinsic antiviral activity of macrophages has been studied in healthy donors and in patients affected by breast cancer and melanoma.In vitro differentiated macrophages from blood-derived monocytes were infected with measles virus, herpes simplex virus type 2 and adenovirus 17. The challenge was carried out with different multiplicities of infection and the synthesis of virus was tested by evaluating the single cycle growth curve in 24 h. The results obtained show that the restriction of virus infectivity by macrophages is strongly influenced by the multiplicity of infection. This was particularly evident with the adenovirus 17. Moreover, macrophages from patients with melanoma and breast cancer showed an impairment of the intrinsic antiviral activity in comparison with normal subjects.

ROLE OF NATURAL RESISTANCE AND IMMUNE RESPONSE IN THE EFFICACY OF ANTIBIOTIC TREATMENT FOR SYSTEMIC SALMONELLOSIS

Salmonella infections are still not declining and cause much morbidity and mortality. For this reason we have looked closely at the action of antibiotics on the host-parasite relationship.

Effect of oral administration of different combinations of killed bacteria on some depressed macrophage functions in tumor-bearing rats

In the present study, we compared the ability of different bacterial species administered orally in various combinations to restore some depressed peritoneal macrophage functions in tumor-bearing rats. Phagocytosis, killing of Candida albicans and chemotactic response of resident peritoneal cells from treated tumor-bearing rats were influenced by different associations of bacteria. In particular, when Staphylococcus aureus was administered together with other bacterial species, the phagocytic activity of peritoneal cells was restored to normal values, and intracellular killing of C. albicans was enhanced. The results are discussed in relation to the possible influence of mucosal bacterial flora on the level of activation of peritoneal macrophages. The possibility that bacterial species can influence in various ways immunocompetent cells in relation to the different chemical composition of some common structures is also discussed.