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Biomedical subjects

A Santoni

Publications and source records attributed to A Santoni.

196 records · Page 11Linked to original sources
PubMedDate not supplied

In vivo cadmium treatment alters natural killer activity and large granular lymphocyte number in the rat.

The effects of oral exposure for nearly 6 months to Cd (200 or 400 ppm) on rat natural killer (NK) activity were investigated. No significant differences in body and thymus weights were observed. Peripheral blood lymphocyte (PBL) number was consistently higher in treated rats throughout the treatment; the number of spleen cells decreased during the first 50 days, and then reached a level higher than in controls. NK activity, evaluated in a 4-h chromium release assay against YAC-1 target cells, was altered in treated rats: lower up to day 30, and then higher. In parallel, a reduction of the large granular lymphocytes (LGL) was found initially in the peripheral blood of Cd-treated rats, followed by a persistent marked increase. These changes were closely correlated with the altered distribution of CD8+ aGM1+ CD5- cells, which mostly consist of NK cells. Fluorescence-activated cell sorter (FACS) analysis revealed a decrease of cell subset with a typical NK phenotype during the first 30 days of treatment and a clear increase thereafter. Post-exposure observations indicated that all these effects disappeared with a return to control values 2 months after cessation of treatment. These findings suggest that in vivo administration of Cd induces both inhibitory and stimulatory effects on rat NK cell number and cytotoxic activity, depending on time of exposure.

Animals↗
PubMedDate not supplied

Cadmium inhibits spontaneous (NK), antibody-mediated (ADCC) and IL-2-stimulated cytotoxic functions of natural killer cells.

Cadmium (Cd2+), an environmental contaminant, has been shown to inhibit, even if not totally, natural killer (NK) cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) of human peripheral blood lymphocytes in a dose- and time-dependent manner. The presence of Cd2+ during the early period of the cytotoxic assay was needed to obtain maximal inhibition. Preincubation of either effector or target cells with Cd did not result in any inhibitory effect. Cd2+ also inhibited the cytotoxic activities of effector cells prestimulated with IL-2 for 18 h or 4 days, which mostly consist of NK cells. Our results indicate that Cd2+ did not block effector-target conjugate formation, but rather interfered with the hydrolysis of phosphoinositides, as shown by the decrease of inositol trisphosphate (IP3), which is known to release stored Ca2+.

Antibody-Dependent Cell Cytotoxicity↗
PubMedDate not supplied

Radiofrequency destruction of the tuberoinfundibular region of hypothalamus permanently abrogates NK cell activity in mice.

Natural killer (NK) cells have an important role in non-adaptative resistance to tumours and their metastatic spread in vivo. Maturation of NK cells and the intensity of their activity are affected by many endogenous and external factors, as well as by regulatory cells. The possibility that some effects of the central nervous system on tumour resistance are mediated via NK activity has also been suggested. Destruction of the tuberoinfundibular region of the hypothalamus in rodents led to a significant increase in tumour growth. We show here that destruction of its ventromedial, dorsomedial and arcuate nuclei persistently abrogates NK activity in mice. By contrast, cortical lesion and operative stress depress it partially, and for a brief period only. Abrogation is the result of a block of NK lineage maturation, causing a severe decrease in the number of large granular lymphocytes (LGL), a lymphocyte population associated with NK activity. Macrophage, B- and T- lymphocyte functions, however, are not significantly affected. Agents inducing NK-cell maturation or activation such as polyinosinic-polycytidylic acid (poly(I:C], interferon (IFN) and interleukin-2 (IL-2) restore NK activity, and normalize the number of LGL.

Animals↗
PubMedDate not supplied

Structure and function of the CC chemokine receptor (CCR) 8.

The CC chemokine receptor (CCR) 8 belongs to the seven transmembrane-spanning receptor family and functionally responds to the eukaryotic CC chemokines I-309, thymus and activation-regulated chemokine, macrophage inflammatory protein-1 beta (MIP-1b) and to the products viral MIP-I and viral MIP-II of the Kaposi-associated herpesvirus (HHV-8). Although it has not yet been fully characterised, its restricted expression to lymphoid tissues, i.e. thymus, spleen and lymph nodes, and its abundant up-regulation in Th2 lymphocytes suggest a potential role in lymphocyte activation, migration and differentiation and in allergic diseases. In this article we review the data known up to now related to CCR8 from cloning to protein structure, expression patterns and functional activation by its agonists.

Amino Acid Sequence↗
PubMedDate not supplied

Polyclonal antibodies against gp185HER2 peptides: their putative role in the identification of a particular HER2 status in patients with breast cancer.

The HER2 oncogene and its relative oncoprotein, gp185HER2, a transmembrane glycoprotein belonging to the epidermal growth factor receptor family, are overexpressed in a wide range of solid tumors including breast and ovarian cancer. In patients with breast cancer, both humoral and cell-mediated HER2 immune responses have been found as well as in some patients with gp185HER2 nonoverexpressing tumors. To establish whether peptide sequences identified as HLA-A2-restricted T-cell epitopes are expressed in breast tumor cell lines and tissues, we produced and characterized by different methodologic approaches polyclonal antibodies raised against four gp185HER2 peptides. Two of the antibodies recognized peptides eluted from the HLA-A2 groove of the mDAmB231 breast cancer cell line expressing a basal level of gp185HER2. Paraffin-embedded primary and metastatic breast tumors were specifically immunostained by all four reagents, thereby showing an overlapping reactivity. When this immunoreactivity was compared with that obtained using two different monoclonal antibodies, in 105 breast primary tumors and 36 corresponding lymph node metastases, we identified a subset of tumors that were negative with anti-gp185HER2 monoclonal antibodies and positive with the four antipeptide antibodies. Our novel observations provide in vivo evidence of the complexity involved in evaluating HER2 expression, and open a new path for understanding the biologic significance of HER2 status in breast tumors.

Amino Acid Sequence↗
PubMedDate not supplied

beta 1-Integrin expression and function in human bladder cancer cells: modulation by TNF alpha.

Cytofluorimetric and biochemical analysis in two different grade human bladder cancer cell lines showed that G3 EJ cells exhibited higher levels of alpha5beta1 and alpha6beta1 heterodimers, and the G2 RT112 cell line higher levels of alpha2beta1. Alpha6/beta4 receptor was detected only in RT112 cells. Adhesion assays with extracellular matrix proteins indicated that both cells bound to fibronectin, laminin and collagen 1, the adhesive properties being related to the integrin profile. Inhibition tests revealed that alpha5beta1 mediated adhesion to fibronectin, alpha3beta1 and alpha6beta1 to laminin, and that alpha2beta1 was the main mediator of adhesion to collagen I in both cell lines. In EJ but not in RT112 cells, tumor necrosis factor-alpha induced the upregulation of alpha2, which mediated increased adhesion to collagen I. The different effects of TNFalpha on the two cell lines were not attributable to differences in tumor necrosis factor responsiveness, as both cells expressed comparable levels of tumor necrosis factor receptor-1 and the tumor necrosis factor-inducible intercellular adhesion molecule-1.

Carcinoma, Transitional Cell↗
PubMedDate not supplied

Interaction of natural killer cells with extracellular matrix induces early intracellular signalling events and enhances cytotoxic functions.

NK cells are endowed with a wide array of adhesion molecules which mediate their interaction with endothelium and extracellular matrix components. We have shown that cross-linking of beta 1 integrins and CD44 on human NK cells induces a signal transduction pathway involving both tyrosine kinase activation and the modulation of intracellular calcium levels. Our studies have also demonstrated the ability of beta 1 integrins and CD44 to upregulate both the spontaneous and the CD16-triggered cytotoxic activity of human NK cells. Although the molecular mechanisms responsible for this costimulatory activity have not been defined yet, our studies indicate that the simultaneous cross-linking of beta 1 integrins and CD44 results in a synergistic effect on CD16-mediated enhancement of intracellular free calcium concentration, and suggest that this may be relevant for the cooperation observed.

Cell Communication↗