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Biomedical subjects

P Puccetti

Publications and source records attributed to P Puccetti.

At least 127 records · Page 7Linked to original sources
PubMed1984

Combined effects of cyclophosphamide and thymostimulin treatment on the in vitro natural killer and candidacidal activity of murine spleen cells.

Two different natural cell-mediated cytotoxic reactions (lysis of YAC-1 and killing of Candida albicans) in vitro were studied in mice undergoing treatment with cyclophosphamide (Cy), thymostimulin (TP-1) or a combination of both. Enhancing effects followed the combination regime in the microbial natural cell-mediated cytotoxicity assay, whereas in the NK assay the effect of TP-1 appeared to be antagonistic to that of Cy. The possible mechanisms involved are discussed.

Animals↗
PubMed1983

Antilymphoma graft responses in the mouse brain: a study of T-dependent functions.

The ability of mouse brain to provide T-dependent antilymphoma graft responses was studied in a model in which graded numbers of tumor cells were implanted intracerebrally into recipient hosts. By using survival criteria, it was possible to demonstrate the occurrence of both primary and secondary responses against tumor-associated histocompatibility antigens in allogeneic models as well as tumor-associated transplantation antigens in histocompatible recipients. The patterns of this intracerebral graft resistance did not differ significantly from those of peripheral T-dependent immune reactivity. The findings are discussed with regard to the concept of the brain as an immunologically privileged site.

Animals↗
PubMed1983

Systemic adoptive immunotherapy of a highly immunogenic murine lymphoma growing in the brain.

Systemic adoptive immunotherapy with specifically immune lymphocytes was successfully performed in immunodepressed mice challenged intracerebrally with L5178Y/DTIC lymphoma cells, a tumor subline rendered highly immunogenic through in vivo exposure to 5-(3,3-dimethyl-1-triazenyl)-IH-imidazole-4-carboxamide (DTIC). The systemic immunotherapy relied on the infusion of the in vitro-generated primary cytotoxic T-lymphocytes (CTL), the anti-tumor activity of which was evaluated by measuring tumor-cell proliferation in the brain in terms of radiolabel uptake and by recording survival times of recipient leukemic mice. The protection afforded by CTL appeared to be specific and was largely conditioned by dose and time of CTL administration. The levels of protection correlated well with the in vitro killing of L5178Y/DTIC tumor cells.

Animals↗
PubMed1983

Correlation between in vivo and in vitro studies of modulation of resistance to experimental Candida albicans infection by cyclophosphamide in mice.

Mice receiving a single injection of cyclophosphamide (150 mg/kg) 1 to 6 days before inoculation with viable Candida albicans showed an increased susceptibility to the challenge accompanied by a reduction in peripheral blood polymorphonuclear leukocytes and lymphocytes as well as in spleen cellularity. Several immunological in vitro functions also appeared to be dramatically depressed. Most of these hematological and functional parameters returned to control values by day 9 after cyclophosphamide administration, at a time when resistance to C. albicans infection appeared to be unchanged. However, when exposure to cyclophosphamide occurred 12 to 21 days before inoculation with the live yeast, enhanced resistance was observed with the majority of the animals surviving challenge. To gain some insight into the mechanisms underlying this late increase in resistance to C. albicans infection after cyclophosphamide administration, we analyzed a series of immunological functions, including the in vitro candidacidal activity of polymorphonuclear neutrophils and plastic-adherent and nonadherent spleen cells as well as the activity of natural killer cells and alloreactive T lymphocytes. The results show that a numerical rebound of blood polymorphonuclear neutrophils and the appearance of a highly candidacidal cell population in the spleen may be among the factors underlying the late increase in resistance to C. albicans after administration of cyclophosphamide.

Animals↗
PubMed1983

Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector.

We have recently reported the in vivo modulation of resistance to experimental Candida albicans infection by cyclophosphamide (150 mg/kg intraperitoneally) in mice and have shown that increased resistance to the microbial challenge occurs 12 to 21 days after treatment with the drug (Bistoni et al., Infect. Immun. 40: 46-55, 1983). The event is accompanied by the appearance of a highly candidacidal cell population in the spleen and the activation of a subpopulation of natural cytotoxic effectors reactive in vitro against YAC-1 tumor cells. We now provide evidence that these anti-YAC-1 cytotoxic effectors are clearly distinct from the cyclophosphamide-induced candidacidal effectors, which seem to belong to a macrophage-monocyte lineage. The enhanced cytotoxic activity induced by cyclophosphamide was not restricted to C. albicans but was also exerted against a panel of Candida strains.

Animals↗
PubMed1983

Phagocytic killing of Candida albicans by different murine effector cells.

Three major phagocytic populations in the mouse were tested in vitro for killing of Candida albicans by means of 51Cr release assay: early inflammatory peritoneal polymorphonuclear cells (PMN), unfractionated or adherent spleen cells and resident peritoneal macrophages (PEC). Considerable candidacidal activity was found in the early inflammatory neutrophil and adherent spleen cell populations. On the contrary, only limited activity was found to be associated with resident peritoneal macrophages. The phagocytic killing apparently involved multiple mechanisms.

Animals↗
PubMed1982

A radiolabel release microassay for phagocytic killing of Candida albicans.

The chromium release technique for quantifying intracellular killing of radiolabelled Candida albicans particles was exploited in a microassay in which murine and human phagocytes acted as effectors under peculiarly simple conditions. At appropriate effector: target ratios and with a 4 h incubation, up to 50% specific chromium release could be detected in the supernatant with no need for opsonization or lysis of phagocytes. This simple microassay permits easy-to-perform, simultaneous testing of a variety of different phagocytes even if only available in limited amounts, and provides an objective measurement of intracellular killing of Candida albicans.

Animals↗
PubMed1982

Cellular mechanisms underlying the adjuvant activity of Candida albicans in a mouse lymphoma model.

Inactivated Candida albicans (CA) possesses strong anti-tumor activity when combined with cytoreductive chemotherapy in a mouse lymphoma model. In the present study, experiments were performed in order to elucidate the mechanism(s) underlying CA immunoadjuvant activity. In vivo chemotherapy studies proved that the synergistic anti-tumor effects were lost in athymic (nu/nu) mice and were also abrogated by radiations. In vitro tests did not suggest a major involvement of natural cytotoxic effectors such as macrophages and natural killer cells nor did CA effects appear to be mediated by induction of interferon. It was concluded that the immunoadjuvant activity of CA largely relies on host responses against tumor-associated transplantation antigens with no major involvement of natural resistance immune mechanisms.

Adjuvants, Immunologic↗
PubMed1981

Depression of hepatic biotransformations by chemical immunoadjuvants.

Administration of BCG and Corynebacterium parvum is known to cause depression of the hepatic microsomal enzyme system (HMES) in mice. In the present study we explored the effects on HMES of two chemical immunoadjuvants, one of which (pyran copolymer) with peculiarly long-lasting biological activities. The two synthetic immunoadjuvants proved to be potent HMES inhibitors and, for pyran copolymer, peak levels of inhibition concurred with maximal macrophage activation. The inhibition was largely dose-dependent and could not be prevented by immunopharmacologic maneuvers that are known to block the C. parvum effect on HMES. The possibility is discussed that common mechanism(s) underlie the depression of HMES by immunoactive substances of both bacterial and chemical origin.

Adjuvants, Immunologic↗
PubMed1981

Drug-mediated increase of tumor immunogenicity in vivo for a new approach to experimental cancer immunotherapy.

In vivo treatment of leukemic mice with the antitumor agent 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) results in early increase of tumor-associated immunogenicity which is expected to evoke host-versus-graft responses. However, transplantation immunity is severely impaired in DTIC-treated mice due to the immunodepressant activity of the drug. It follows that the DTIC-mediated increase of tumor immunogenicity effect cannot be of therapeutic value in ordinary conditions. In the present report, we describe the results of studies aimed at restoring immunocompetence of DTIC-treated mice by means of adoptive transfer of syngeneic lymphoid cells. Infusion of spleen cells into DTIC-treated mice failed to restore graft responsiveness even in allogeneic tumor-host combinations. However, when DTIC treatment was followed by administration of cytotoxic alkylating agents such as cyclophosphamide (CY) or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), graft responsiveness was partially restored upon adoptive transfer of syngeneic splenocytes. (BALB/c X DBA/2) F1 (hereafter called CD2F1) mice bearing leukemia L1210 Ha were treated as follows: (a) DTIC for increasing the immunogenicity of the leukemic cells; (b) CY or BCNU; and (c) adoptive transfer of CD2F1 lymphocytes. The results showed that: (a) DTIC alone or DTIC plus spleen cells produced little or no increase in survival times with respect to untreated controls; (b) DTIC plus CY or BCNU increased survival times to a larger extent; and (c) the adoptive transfer of lymphocytes produced marked protection of leukemic mice when the hosts had been pretreated with DTIC plus CY or BCNU but not with CY or BCNU without DTIC. These data may provide a model for exploiting DTIC-induced increase of tumor immunogenicity for immunochemotherapeutic regimens.

Animals↗
PubMed1980

Cytotoxic effector cells with the characteristics of natural killer cells in the lungs of mice.

Cells with in vitro cytotoxicity against tumor targets in a short-term 51Cr release assay have been recovered from the lungs of mice that were either untreated or injected with biological or synthetic agents 1--3 days earlier. The cytotoxic effector cells were non-adherent, non-phagocytgic and shared many characteristics with splenic natural killer (NK) cells. This finding is discussed with particular regard to our previous observations on the rapid in vivo elimination from the lungs of intravenously injected, radiolabelled tumor cells.

Adjuvants, Immunologic↗
PubMed1979

Activation of mouse macrophages by pyran copolymer and role in augmentation of natural killer activity.

Inoculation of mice with pyran copolymer resulted in activation of natural killer (NK) cells as well as macrophages. Conditions optimal for the boosting of NK activity seemed to differ from those optimal for macrophage activation as assessed by cytostasis of tumor target cells. Peak levels of macrophage cytostatic reactivity were found at about 7 days after drug injection and were only achieved by the highest doses of pyran tested. Macrophage activation was consistently higher in the peritoneal cavity than in the spleen, regardless of route of administration, in contrast to the failure of i.v. pyran to induce high NK reactivity in peritoneal exudate cells. At 2-3 days after pyran treatment of older mice, NK augmentation reached peak levels, but only minimal macrophage activation was found. Despite these differences, macrophages played a role in regulating NK activity in pyran-treated mice. Functional macrophages appeared to be required for augmentation of NK activity by pyran, since boosting was impaired by prior in vivo inoculation of silica. Macrophages also appeared able to inhibit NK activity. In younger mice that exhibited high spontaneous levels of NK activity, pyran treatment produced a substantial reduction in NK activity to levels below those of untreated mice. This depression coincided with the time of peak levels of macrophage cytostasis. Furthermore, removal of adherent cells from the spleen cells of these pyran-treated mice resulted in levels of NK activity almost as high as those of untreated mice. The possibility that the depression of NK activity in young mice by pyran copolymer is due to suppressor cells is discussed.

Animals↗
PubMed1979

Augmentation of natural killer activity by pyran copolymer in mice.

Treatment of older mice with pyran copolymer, a known interferon-inducer, was found to result in a rapid boosting of cell-mediated cytolytic activity against YAC-1 tumor target cells. The effector cells were characterized as being non-adherent and were presumed to be natural killer (NK) cells. Augmentation occurred in various lymphoid organs and was detectable 2-3 days after drug treatment. Differences in the levels of boosted activity among the lymphoid organs resulted when the route of administration was varied. The degree of augmentation was largely independent of the dose of pyran, but did vary among different strains of mice. Augmentation, moreover, was followed by a rapid decline by 5-7 days.

Adjuvants, Immunologic↗