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Biomedical subjects

A Cossarizza

Publications and source records attributed to A Cossarizza.

At least 127 records · Page 7Linked to original sources
PubMed1991

Cytotoxicity and immunocyte markers in cells from the freshwater snail Planorbarius corneus (L.) (Gastropoda pulmonata): implications for the evolution of natural killer cells.

The hypothesis that natural killer (NK) cells represent an important form of cell recognition and cytotoxicity leads to the prediction that NK-like activity should be preserved throughout phylogenetic development. This was tested in the invertebrate Planorbarius corneus. Two types of cells can be identified and separated from the hemolymph of this mollusc, i.e. glass-adherent macrophage-like spreading hemocytes (SH) and nonadherent round hemocytes (RH). Only RH are able to lyse the K-562 human target cell line in a short-term NK cytotoxicity test. This NK-like activity, severely reduced after 18 h incubation at 24 degrees C, is preserved by human recombinant interleukin 2. A further analysis of P. corneus hemocytes has been performed by using several mouse anti-human monoclonal antibodies and cytofluorimetric analysis. Unexpectedly, both SH and RH react with several monoclonal antibodies, including those directed against epitopes typical of mammalian NK cells and cell adhesion molecules. On the whole, these data support the hypothesis that a primitive NK-like activity appeared early in evolution and is not shared by phagocytic cells.

Animals↗
PubMed1991

Preferential expression of V beta 6.7 domain on human peripheral CD4+ T cells. Implication for positive selection of T cells in man.

The peripheral T cell receptor repertoire is mainly controlled by the processes of positive and negative selection occurring in the thymus. Studies in normal or transgenic mice have provided compelling evidence for both negative and positive selection. Negative selection is characterized by partial or total disappearance from the periphery of T cells expressing certain C beta regions, which are normally present in the thymus. Positive selection is chiefly characterized, in the periphery, by an imbalanced ratio between CD4+ and CD8+ T cells expressing a given V domain. To date little information concerning positive and negative selection has been available in man. We studied the distribution of 4 V beta domains on CD4+ and CD8+ peripheral T cells of 34 healthy individuals with a wide age-range (0-96 years). One of the V beta domain studied, V beta 6.7, is preferentially expressed on CD4+ compared to CD8+ T cells (p greater than 0.001). No significant differences were observed using the other V beta domain-specific monoclonal antibodies (V beta 5.2-5.3, 8 or 12). These results provide evidence that a process of thymic education, similar to that described in murine animal models, may also take place in man.

Adult↗
PubMed1991

Exposure to low-frequency pulsed electromagnetic fields increases mitogen-induced lymphocyte proliferation in Down's syndrome.

We previously reported that exposure of human mitogen-stimulated peripheral blood lymphocytes (PBL) to extremely low frequency pulsed electromagnetic fields (PEMFs) could restore the defective proliferative capability of PBL from aged subjects. The effects of exposure to PEMFs were studied in PBL from 25 patients with Down's syndrome (DS), a syndrome of premature aging characterized by precocious immune system derangement, including age-related defective PBL proliferative capability. PBL were stimulated with different doses of phytohemagglutinin, and cell proliferation was assessed by measuring the incorporation of tritiated thymidine. After PEMF-exposure, a significant increase in cell proliferation was observed in cells from DS children and young adults, but it was much more evident in PBL from relatively aged DS patients. The age-related effect of PEMFs on DS lymphocytes demonstrates that age must be considered a major variable when studies on DS are performed, and confirms that DS must be regarded as a syndrome of accelerated aging.

Adolescent↗
PubMed1991

Inhibin and activin modulate human monocyte chemotaxis and human lymphocyte interferon-gamma production.

Inhibin and activin are referred to as gonadal glycoprotein hormones whose function is the control of FSH release from the pituitary gland. However, several observations indicate that inhibin and activin are produced in various organs and serve multiple functions. Because bone marrow and spleen produce inhibin and activin, our aim was to evaluate their possible effect on cell-mediated immune function. For this reason we studied 1) monocyte chemotaxis, 2) lymphocyte interferon-gamma production, 3) phytohemagglutinin-induced lymphocyte proliferation, and 4) nonmajor histocompatibility complex-restricted and lymphokine-activated lymphocyte cytotoxicity. All studies were performed on human peripheral blood cells in the absence or presence of various doses of inhibin, activin, or inhibin plus activin. A significant dose-related increase in monocyte chemotaxis was induced by inhibin. Activin increased the migrational activity of monocytes, but via random, not directed, migration. Inhibin significantly decreased interferon-gamma production, and its effect was reversed by activin. Inhibin and/or activin had no significant effect on either phytohemagglutinin-induced lymphocyte proliferation or lymphocyte cytotoxic capability. The present demonstration that inhibin and activin may affect some immune parameters suggests a possible involvement of these hormones in regulating cell-mediated immune function.

Activins↗
PubMed1991

Effect of low frequency low energy pulsing electromagnetic fields on mice injected with cyclophosphamide.

C3H mice have been used to investigate the effect of a combination of cyclophosphamide (CY) and electromagnetic fields (PEMF). Mice were injected i.p. with a single dose of 200 mg/kg body weight of CY and then exposed to PEMF 24 h per day. In an initial series of experiments immediately after CY injection mice were exposed to PEMF until sacrifice. WBC counts in the peripheral blood demonstrated a quicker decline in WBC at days 1 and 2 in mice exposed to PEMF. Groups of mice were sacrificed at days 1, 4, 6, 8, and 10 after CY injection. In mice exposed to PEMF the spleen weight was less than in controls at days 6, 8, and 10. Autoradiographic studies demonstrated that the labeling index of bone marrow smears did not significantly differ between controls and experimental mice exposed to PEMF, whereas the spleen labeling index proved to be higher among control mice versus mice exposed to PEMF at day 6, and higher among mice exposed to PEMF versus controls at day 8. In a second series of experiments mice were exposed to PEMF only over the 24 h following CY injection. We found that the spleens of mice exposed to PEMF weighed less than those of controls at days 6 and 8. The labeling index of bone marrow did evidence a slight decrease among mice exposed to PEMF at days 8 and 10 after CY injection versus control mice. The spleen labeling index proved to be lower in experimental mice exposed to PEMF than in controls at days 4, 6, and 8. Mice were then injected with CY, half were exposed to PEMF, and 24 h later bone marrow was recovered from both groups of animals. The same number of bone marrow cells was injected via the tail vein into recipient mice irradiated to 8.5 Gy. The grafting efficiency of the bone marrow was evaluated by examining the number of spleen colonies and the spleen and bone marrow labeling indices at day 8; all parameters proved to be significantly lower among mice grafted with the bone marrow of mice injected with CY and exposed to PEMF than among controls injected with CY only. Finally, we found th at the effect of PEMF is evident only if mice are exposed during the 24 h following CY injection. The data reported here indicates that PEMF exposure after CY injection increases the damage induced in mice by CY.

Animals↗
PubMed1990

Immunocytochemical evidence of vertebrate bioactive peptide-like molecules in the immuno cell types of the freshwater snail Planorbarius corneus (L.) (Gastropoda, Pulmonata).

An immunocytochemical investigation was carried out on round and spreading hemocytes of Planorbarius corneus by using 20 antisera to vertebrate bioactive peptides. The immunotests showed the presence of alpha 1-antichymotrypsin-bombesin-, calcitonin-, CCK-8 (INC)-, CCK-39-, gastrin-, glucagon-, Met-enkephalin-, neurotensin-, oxytocin-, somatostatin-, substance P-, VIP-, and vasopressin-immunoreactive molecules in the spreading hemocytes. The round hemocytes were only positive to anti-bombesin, anticalcitonin, anti-CCK-8 (INC), anti-CCK-39, anti-neurotensin, anti-oxytocin, anti-substance P and anti-vasopressin antibodies. No immunostaining was observed with anti-CCK-8 (Peninsula), anti-insulin, anti-prolactin, anti-thyroglobulin and anti-thyroxin (T4) antibodies. As probably in vertebrates, these bioactive peptides may modulate immuno cell function.

Animals↗
PubMed1990

Precocious aging of the immune system in Down syndrome: alteration of B lymphocytes, T-lymphocyte subsets, and cells with natural killer markers.

Phenotype and proliferative ability of peripheral blood lymphocytes from 15 noninstitutionalized children affected with Down Syndrome (DS), in apparently good health, were studied and compared with those of 16 healthy control children of the same age. A complex derangement of all the major peripheral blood cell subsets, i.e., B cells, T cells, and natural killer (NK) cells, was present in DS children. A significant decrease of the absolute number of circulating lymphocytes, a marked and significant decrease of B lymphocyte absolute number and percentage, and dramatic modifications of the T-cell subsets were observed. The absolute number of CD4+ cells was significantly decreased, whereas CD8+ cells increased significantly in percentage but not in absolute number. A derangement of cells bearing markers associated with NK activity, such as CD57, CD16, and CD56, was observed. Among the most important alterations, the presence of a high number of CD57+, CD16- cells, of CD57+, CD8+ lymphocytes, and of CD3+, CD56+ lymphocytes was seen. Many of these alterations are similar to those characteristic of chromosomally normal subjects of advanced age. The hypothesis that the reduced thymic endocrine activity and the zinc deficiency characteristic of DS are responsible for the derangement of T and NK subsets is discussed.

Adolescent↗
PubMed1990

LAK activity is inducible in blood mononuclear cells from human fetus.

Lymphocyte subpopulations, NK and LAK activities have been studied in blood mononuclear cells from two human fetuses, the first affected by Down's syndrome, the other showing a normal karyotype. Fetuses presented similar subsets, with a scarcity of CD57+ lymphocytes but an appropriate amount of CD16+ and CD56+ cells, while negligible NK activity was detectable. After 18 h of incubation with human recombinant interleukin-2 (rIL-2), significant enhancement of the cytotoxic capability was observed. This stresses the role of IL-2 as a regulatory molecule during the development of the immune system in the human fetus.

Adult↗
PubMed1990

Presence of ACTH and beta-endorphin immunoreactive molecules in the freshwater snail Planorbarius corneus (L.) (Gastropoda, Pulmonata) and their possible role in phagocytosis.

The presence of ACTH and beta-endorphin immunoreactive molecules in the cell-free hemolymph and in the hemocytes of the freshwater snail Planorbarius corneus were demonstrated by immunocytochemistry and RIA tests. Only spreading phagocytic hemocytes were positive, in contrast with other hemocytes devoid of phagocytic activity, i.e., round hemocytes. These data were confirmed by flow cytometry. Another cell type with marked phagocytic activity, i.e., digestive cells of digestive gland, were also positive to anti-ACTH. Corticotropin-releasing factor immunoreactive molecules were found in the cell-free hemolymph and hemocytes, by RIA. Our data suggest that cells with phagocytic activity, the oldest immune response, may represent a suitable model to unravel the tangled web of the common ancestor of the immune and the neuroendocrine systems.

Adrenocorticotropic Hormone↗
PubMed1990

Recovery of human lymphocytes damaged with gamma-radiation or enzymatically produced oxygen radicals: different effects of poly(ADP-ribosyl)polymerase inhibitors.

Quiescent human lymphocytes were damaged in two different ways, both producing toxic oxygen radicals: xanthine oxidase plus hypoxanthine (XOD/HYP), or gamma-rays. Under conditions where DNA synthesis was reduced to 10-20% of control, inhibitors of poly(ADP-ribosyl)polymerase (ADPRP, an enzyme that becomes activated in the presence of DNA strand breaks) allowed lymphocytes to recover completely when the damage was caused by XOD/HYP, but they did not affect DNA synthesis of irradiated cells. However, a protective effect of ADPRP inhibitors was observed with irradiated lymphocytes receiving doses greater than or equal to 50 Gy. Unscheduled DNA synthesis was Unscheduled DNA synthesis was significantly increased when lymphocytes were damaged by high radiation doses in the presence of ADPRP inhibitors. We suggest that ionizing radiation does not stimulate poly(ADP-ribose) synthesis in lymphocytes at doses that impair lymphocyte DNA synthesis by 80-90%, while ADPRP may be involved in the repair of DNA lesions occurring at higher radiation doses.

DNA Repair↗
PubMed1990

Immunological parameters in aging: studies on natural immunomodulatory and immunoprotective substances.

Several immune parameters--particularly T-cell dependent immune responses--are altered in aged subjects. To test the hypothesis that they may be the consequence of more general age-related lymphocyte biochemical alterations, and particularly of the energy producing system, the effect of L-carnitine and acetyl-L-carnitine on cell proliferation was studied in peripheral blood lymphocytes from donors of different ages. The results showed that phytohaemagglutinin-induced peripheral blood lymphocyte proliferation was markedly increased in L-carnitine- or acetyl-L-carnitine-preloaded lymphocytes from young and especially from old subjects. Cells from aged subjects considerably improved their defective proliferative capability. Preliminary observations suggest that L-carnitine-preloading also protected peripheral blood lymphocytes from old donors when such cells were exposed to an oxidative stress.

Acetylcarnitine↗
PubMed1989

Inhibition of poly(ADP-ribosyl)ation does not prevent lymphocyte entry into the cell cycle.

The enzyme poly(ADP-ribosyl)transferase (ADPRT) becomes activated soon after a mitogenic stimulus is applied to lymphocyte cultures. It has also been reported that ADPRT inhibitors prevent cell proliferation when added to cultures at the same time as the mitogen. While this has been ascribed to the need to seal physiologically present DNA strand breaks before cells enter S phase, the presence of DNA strand breaks in quiescent human lymphocytes has been recently questioned. We demonstrate here that non-toxic concentrations of ADPRT inhibitors do not affect lymphocyte blastization and proliferation, as measured by thymidine incorporation and cytofluorimetry. We therefore suggest that ADPRT activation is required for late functions which are not needed for cell cycle progression.

Benzamides↗
PubMed1989

Extremely low frequency pulsed electromagnetic fields increase interleukin-2 (IL-2) utilization and IL-2 receptor expression in mitogen-stimulated human lymphocytes from old subjects.

The effects of the exposure of mitogen-stimulated human lymphocytes from aged subjects to low-frequency pulsed electromagnetic fields (PEMFs) were studied by measuring the production of interleukin-2 (IL-2) and the expression of IL-2 receptor. PEMF-exposed cultures that presented increased [3H]thymidine incorporation showed lower amounts of IL-2 in their supernatants, but higher percentages of IL-2 receptor-positive cells and of T-activated lymphocytes. Taken together, these data suggest that PEMFs were able to modulate mitogen-induced lymphocyte proliferation by provoking an increase in utilization of IL-2, most likely acting on the expression of its receptor on the plasma membrane.

Aged↗
PubMed1989

Extremely low frequency pulsed electromagnetic fields increase cell proliferation in lymphocytes from young and aged subjects.

The effect of the in vitro exposure to extremely low frequency pulsed electromagnetic fields (PEMFs) on the proliferation of human lymphocytes from 24 young and 24 old subjects was studied. The exposure to PEMFs during a 3-days culture period or during the first 24 hours was able to increase phytohaemagglutinin-induced lymphocyte proliferation in both groups. Such effect was greater in lymphocytes from old people which showed a markedly reduced proliferative capability and, after PEMF exposure, reached values of 3H-TdR incorporation similar to those of young subjects. The relevance of these data for the understanding and the reversibility of the proliferative defects in cells from aged subjects and for the assessment of risk related to the environmental exposure to PEMFs has to be considered.

Adult↗
PubMed1989

Diverse effects of three furocoumarins on human lymphocyte proliferation.

The biological effects of three furocoumarins on the proliferation of human normal peripheral blood lymphocytes have been investigated. Mitogen-stimulated human lymphocytes were assayed "in vitro" by measuring 3H-thymidine (3H-TdR) incorporation in the presence and in the absence of 15-30 microM 3-carbethoxypsoralen (3-CPs), trimethylangelicin (TMA) and psoralen (PSR) with and without UV-A irradiation (365 nm). The three furocoumarins differ in their ability to form mono- and bi-functional adducts with DNA pyrimidine bases and in producing reactive species of oxygen. At low furocoumarin doses and short times of UV-A irradiation (15-30 sec) used in the present study, 3-CPs did not affect 3H-TdR incorporation in PHA-stimulated human lymphocytes, TMA strongly inhibited 3H-TdR incorporation, while, unexpectedly, PSR increased 3H-TdR incorporation in the absence of irradiation, likely acting, under these experimental conditions, as a co-mitogen.

Ficusin↗