Biomedical subjects
Publications and source records attributed to K Resch.
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Purified human blood lymphocytes were stimulated with concanavalin A or phytohemagglutinin. DNA synthesis was measured with 2-h pulses of [3H]thymidine between 48 h and 73 h after stimulation. Colchicine, at concentrations between 0.1 muM and 10 muM, suppressed consequent DNA synthesis without affecting viability of the cells when added at any time up to 18 h before incorporation of [3H]thymidine was assessed. In concanavalin-A-stimulated lymphocytes, removal of the mitogen by methyl alpha-mannoside only prevented proliferation when added initially, but was without any effect when added after 20 h of stimulation, regardless of when DNA synthesis was measured. Thus, there was a period after 20 h of concanavalin A stimulation, when DNA synthesis was still sensitive to colchicine, but no longer required the presence of the mitogen. Colchicine also suppressed incorporation of [3H]leucine into protein, in resting as well as mitogen-stimulated lymphocytes. Similarly, colchicine decreased amino acid transport, as determined by uptake of alpha-amino-isobutyrate, which appeared to be the rate-limiting step in the incorporation of amino acids into protein in colchicine-treated cells. When the rate of protein synthesis was followed by the relative distribution of ribosomal particles, especially the increase of polysomes in activated lymphocytes, colchicine was without any detectable effect. The early increase in the incorporation of [14C]oleate into phospholipids was identical in the presence or absence of the microtubule-active drug. The data strongly suggest that microtubules are not involved in the initiation of lymphocyte growth or mitogenesis.
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We have investigated the proliferative response and interferon production in cultures of mouse thymocytes stimulated with two different mitogens, PHA (phytohemagglutinin), or Con A (concanavalin A). Normal thymocytes proliferated weakly and did not produce detectable interferon levels in response to both mitogens. Supplementing this cell population with macrophages or adding 2-mercaptoethanol to the culture medium strongly enhanced the proliferative response to both mitogens, but only in response to PHA marginal levels of interferon could be detected. When the steroid-resistant population was tested, both PHA and Con A induced strong proliferative responses; in this case significant interferon levels could be obtained after stimulation with PHA, but only borderline levels with Con A. Peripheral lymphocytes from the spleen responded identically to both mitogens with respect to interferon production as well as proliferation. The data suggest that distinct differentiation pathways may exist for T lymphocytes producing interferon in response to different mitogens.
Rat peritoneal macrophages released high amounts of prostaglandin E (PGE) when treated in vitro with 10(-7) to 10(-4) M colchicine. PGE production occurred after a lag period of 4 hr and proceeded at a constant rate for more than 24 hr. Lymphocytes could not be stimulated to PGE release by colchicine. Disaggregation of microtubules appeared to be an essential event, since lumicolchicine was inactive and addition of heavy water (D2O) abolished colchicine-induced PGE formation. Cytochalasin B (5 microgram/ ml) did not interfere with PGE production by colchicine during the initial 12 hr, but thereafter it gave rise to an activity capable of degrading or converting newly synthesized PGE. Although details of the mechanisms by which colchicine in association with disrupted microtubules may induce PGE release remain unclear, these observations suggest that components of the cytoskeleton may efficiently influence the biosynthesis of prostaglandins.
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Human mononuclear cells from peripheral blood which were treated with phospholipase C (PLC), became cytotoxic against human or chicken red blood cells. PLC-induced cellular cytotoxicity against human red blood cells was further analyzed and compared to anti-D-mediated, antibody-dependent cellular cytotoxicity (ADCC), using the same target cells. ADCC, but not cytotoxicity of PLC-treated effector cells, was inhibited by free IgG. In addition, iodoacetate strongly enhanced PLC-induced cytotoxicity, but blocked ADCC completely. Addition of fetal calf serum or human AB serum impaired PLC-induced cytotoxicity. A similar inhibition was found by adding lecithin liposomes suggesting that the inhibitory effect of sera was also due to their phospholipid content. The data show that cytotoxicity of PLC-treated effector cells can be clearly distinguished from cellular cytotoxicity, occurring spontaneously or induced by target cell antibodies. We favor the notion that cytotoxicity of PLC-treated effector cells against human erythrocytes is due to the action of PLC, adsorbed to the effector cells.
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