Biomedical subjects
Publications and source records attributed to E Crivellato.
A 67-year-old male patient, with a history of palmar psoriasis for 8 years, developed a rosacea-like eruption during Tigason (Ro-10-9359) treatment. Strict relationship between Tigason intake and skin symptoms was proved by double introduction of the drug and the patient's previous history. This retinoid side effect is very unusual and we are unable to give any explanation for it.
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P-glycoprotein has been identified in mast cells stabilized in culture as well as in rat peritoneal mast cells, and is primarily concentrated on the granular membrane. This study aimed to define the role of this protein in the transport and accumulation of doxorubicin in mast cell granules and in its histamine releasing effect. The reverting agent verapamil, that is a substrate for P-glycoprotein, inhibited doxorubicin uptake in intact mast cells in a dose and time dependent manner, but had no effect on the exocytotic action of the antineoplastic drug. Doxorubicin was also concentrated in granules with intact membranes and the uptake was dependent on temperature and showed a trend for saturation. Verapamil and vinblastine, another substrate for P-glycoprotein, significantly reduced doxorubicin concentrations in intact granules. Similar results were obtained with the metabolic inhibitors sodium metavanadate, N-ethylmaleimide, and sodium azide, whereas ouabain, an inhibitor of sodium-potassium ATPase, was without effect. Doxorubicin was taken also up in granule remnants, consisting of a proteoglycan matrix without membrane, that are extruded from mast cells upon stimulation. However, the uptake was not dependent on temperature and was not modified by P-glycoprotein substrates or metabolic inhibitors. Rat peritoneal mast cells were examined for the expression of P-glycoprotein at the protein level with C219 monoclonal antibody, using Western blot, confirming that P-glycoprotein was expressed in mast cells. These data suggest the presence of a P-glycoprotein active in the transport of doxorubicin, in mast cell granules.
It has recently been shown that adriamycin is accumulated in mast cells by an active transport system, which closely resembles the outward transport system of multidrug resistant (MDR) cells. The present study was undertaken in order to test the effect of substances which are known to limit or reverse resistance in MDR cells on adriamycin uptake and histamine release in rat peritoneal mast cells. The lysosomotropic amines chloroquine, nicotine, propranolol, atropine, methylamine, ammonium chloride and quinacrine were only slightly effective at very high concentrations; no effect could be observed with the lysosomotropic amine amantadine. The carboxylic ionophores monensin and nigericin were, on the contrary, extremely efficacious; in particular, the effect of monensin was more evident when mast cells were preincubated with the ionophore for 10 or 30 minutes while only a slight inhibition was evident when the two substances were added simultaneously. Removal of monensin from the incubation medium before challenge with adriamycin did not abolish the inhibitory action of the ionophore. Among the tested membrane active agents, Tween 80 and Triton WR-1339 were able to limit adriamycin uptake and histamine release. The microscopical examination showed that in mast cells treated with adriamycin, an intense fluorescence was present in cytoplasmic granules; on the contrary, mast cells preincubated with monensin showed hardly any fluorescence.
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The in vivo three-dimensional architecture of lymph node and spleen interdigitating cells (IDCs) has been studied in mice by means of a computer reconstruction program and polystyrene models. Tissue fragments treated with an osmium-zinc iodide fixative solution, which gives a brilliant and quite specific impregnation of IDCs, were embedded in Epon and cut into 2 microns thick serial sections. The data was transferred into a "MOP-Videoplan 3D-cell reconstruction" software program and both tridimensional plottings and morphometric measurements were obtained. Then polystyrene models were assembled. Our findings show a cell population of high spatial complexity. IDCs are large cells whose numerous cytoplasmic processes form an extensive three-dimensional network which envelopes lymphoid cells. The most characteristic feature of IDC' architecture is the large, flattened, sheet-like processes which expand for several microns from the cell body, embracing numerous lymphocytes and lymphoblasts. In certain cases surface invaginations create channel-like structures which cross through the IDC peripheral cytoplasm. The impressive extension of the IDC membranous network provides a powerful anatomic strategy which facilitates the interaction between IDCs and T-lymphocytes and creates a unique microenvironment for T-cell activation and proliferation. This study gives new morphological evidence for the strict physical interaction between IDCs and T-lymphocytes and supports the concept that IDC-T lymphocyte aggregation represents a very special microanatomical and functional unit.