Search PubMed⌕ Search

Biomedical subjects

K Resch

Publications and source records attributed to K Resch.

At least 199 records · Page 11Linked to original sources
PubMed1978

Antibody dependent cellular cytotoxicity (ADCC) against human erythrocytes, mediated by blood group alloantibodies: a model for the role of antigen density in target cell lysis.

Antibody dependent cellular cytotoxicity (ADCC) of human mononuclear cells against human erythrocytes could be obtained with anti-A and anti-D sera. The degree of lysis varied considerably depending on the antigen system and on the experimental conditions. Anti-D mediated in contrast to anti-A mediated ADCC turned out to be very sensitive to conditions which interfere with target cell lysis: for most of the anti-D sera, removal of unbound IgG was found to be crucial to detect their ability to mediate ADCC. Pretreatment of the target cells with various enzymes dramatically improved specific lysis and left spontaneous release and spontaneous cytotoxicity essentially unaffected. In the case of neuraminidase treatment it could be shown that the effect was independent from the exposure of additional binding sites. When enzyme treatment and removal of excess IgG were applied in combination, as little as 10(4) antigenic determinants proved to be sufficient to induce specific lysis.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

Enhancement of the PGE1 response of macrophages by concanavalin A and colchicine.

The effect of concanavalin A (Con A) and colchicine on the prostaglandin E1 (PGE1)-mediated cyclic AMP generation in rat peritoneal macrophages have been studied. Although Con A and colchicine by themselves did not affect cyclic AMP levels, they greatly enhanced cyclic AMP production induced by PGE1. There was not only augmentation of cyclic AMP levels at maximally active concentrations of PGE1, but also an increased sensitivity to low (inactive) concentrations of PGE1. Except for lentil lectin, none of the other lectins affected PGE1 sensitivity whereas lumicolchicine was as effective as colchicine. In addition, both Con A and colchicine raised the sensitivity to isoproterenol and choleraenterotoxin. Although details of the mechanisms by which Con A or colchicine influenced the membrane-bound adenyl cyclase and PGE1 receptors remain unclear, these observations suggest that certain alterations of the cell membrane may render macrophages more susceptible to the regulating effects of prostaglandins.

Adenylyl Cyclases↗
PubMed1977

Induction of lymphocyte proliferation and membrane changes by lipopeptide derivatives of the lipoprotein from the outer membrane of Escherichia coli.

Lipoprotein from the outer membrane of E. coli, a potent novel mitogen, was digested by pronase treatment resulting in lipopeptide fragments containing 2-5 amino acids bound to diacylglyceryl-N-acylcysteinthioether. The lipopeptides were characterized by amino acid analysis and gas chromatography and were checked for mitogenicity. We found that all lipopeptide fragments were able to stimulate the uptake of 3H-uridine into RNA and 3H-thymidine into DNA in mouse spleen cells of several strains. The response of splenocytes of congenitally athymic mice was comparable to that of normal animals. A weak stimulation of DNA synthesis was also observed in thymocytes. The mitogenicity of the products was abolished by mild alkali hydrolysis which removes the ester-bound fatty acids. We conclude that the N-terminal lipopeptide region of lipoprotein is responsible for the mitogenic activity of the molecule. Lipopeptide as well as lipoprotein were found to cause early membrane changes in lymphocyte plasma membranes. After 4 hours we found an increased incorporation of 14C-oleate and 14C-acetate into lecithin. The membrane changes observed are similar to those brought about by mitogenic lectins, which suggests a similar mechanism for the induction of lymphocyte activation for both types of mitogens.

Amino Acids↗
PubMed1976

Phospholipid metabolism of stimulated lymphocytes. Comparison of the activation of acyl-CoA:lysolecithin acyltransferase with the binding of concanavalin A to thymocytes.

Calf thymocytes were isolated and incubated with concanavalin A. The effect of the mitogen on the enzyme activity of membrane-bound lysolecithin acyltransferase (acyl-CoA:1-acylglycero-3-phosphorylcholine-O-acyltransferase, EC 2.3.1.23) was determined as also the binding of 125I-labelled concanavalin A to intact cells and isolated membranes. The lysolecithin acyltransferase was found to be activated three times in microsomal membranes. The activation occurred directly after binding of concanavalin A and was temperature independent, since similar activities were found in cells treated with concanavalin A at 0 and 37 degrees C. The acyltransferase activation using increasing concentrations of concanavalin A revealed a different behaviour, as compared to the binding of concanavalin A. While the binding of concanavalin A to intact cells expressed a normal hyperbolic saturation function the activation process of the acyltransferase described a sigmoidal relationship. Correspondingly, the interaction coefficients for both functions were different (Sips coefficient for binding = 1.0 and Hill coefficient of the enzyme activation = 1.8). These results indicate that the acyltransferase activation is due to a cooperative interaction between the ligand-receptor complex and the enzyme.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1976

Initial stages of differentiation of thymocytes in the plasma membrane.

There is some evidence in the plasma membrane after binding of molecules triggering differentiation processes that different membrane areas exist possessing different functions. We have tried to isolate these different membrane areas, using a type of affinity chromatography on Con A-Sepharose. Our results from binding sites, affinity constant and fatty acid composition seem to reinforce the evidence that heterogeneous plasma membrane areas exist having different functions in the proliferation and differentiation process of thymocytes after triggering with Con A.

Acyltransferases↗
PubMed1976

Mitogen-induced membrane changes and cell proliferation in T lymphocyte subpopulations.

Rabbit thymus-dependent lymphocytes were exposed to phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) or anti-immunoglobulin at various stages of maturation. Proliferation (induction of DNA synthesis) and early membrane events (turnover of membrane phospholipids) were measured in neonatal thymocytes, normal adult thymocytes, prednisolone-resistant thymocytes and lymph node lymphocytes. In immature thymocytes PHA induced only a marginal increase in DNA synthesis. The mitotic response increased with maturation, but only peripheral T lymphocytes exhibited maximum stimulation. Con A and PWM were able to induce DNA synthesis in immature thymocytes and the degree of stimulation was shown to increase with maturation. In contrast to the different degree of proliferation of thymocytes induced by PHA or Con A the incorporation of [14C]oleate, [14C]choline or [14C]acetate into phospholipids was stimulated to the same degree by these lectins. Reactivity of T lymphocytes, as measured by early membrane changes at different stages of maturation, to different T cell mitogens appears to be identical. Differences in degree of cell proliferation therefore may be secondary phenomena due, in part, to tissue culture conditions. Reactivity to mitogens as measured by phospholipid turnover appears to be an early acquired function in the maturation of lymphocytes of the T cell line.

Animals↗
PubMed1976

[Phospholipid metabolism in transformed lymphocytes. Molecular mechanism of activation].

An early consequence of lymphocyte stimulation by mitogens is the increased turnover of phospholipid fatty acid moieties. The enzymes catalyzing the selective transfer of fatty acids exhibit a high affinity for highly unsaturated fatty acids. The activation of these acyltransferases leads to a higher content of polyenoic fatty acids and consequently to an increased membrane fluidity.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1976

The inhibition of initial steps of lymphocyte transformation by cytochalasin B1.

CB was shown to inhibit the PHA-induced activation of rabbit lymph node lymphocytes as assessed by the incorporation of 3H-uridine into RNA or 3H-thymidine into DNA. This suppression was dose dependent with an optimum of 10 mug CB/ml (20, 8 muM). Mitogen-activated lymphocytes escaped the inhibitory effect of the drug when CB was added later than 1 hr after the addition of PHA. CB also suppressed the activation of membrane phospholipid metabolism which occurs among the earliest detectable changes in activated lymphocytes. Thus the incorporation of 14C-choline, 14C-acetate, or 14C-oleate into lecithin in the presence of PHA and CB was the same as the level of their incorporation in unstimulated lymphocytes. The increased incorporation of 14C-oleate into lecithin of the plasma membrane of activated lymphocytes was similarly prevented in the presence of CB. In contrast, CB exhibited no or only a marginal effect on the phospholipid turnover of unstimulated lymphocytes. Our results point to plasma membrane phospholipid metabolism as the possible site of CB interference with the lymphocyte activation.

Animals↗
PubMed1975

Phospholipid metabolism of stimulated lymphocytes. Composition of phospholipid fatty acids.

Lymph node lymphocytes and thymocytes from different species were isolated. Rabbit and calf thymocytes were stimulated in vitro with concanavalin A. Phospholipid fatty acids of these cells were analyzed and their positional distribution was determined. When compared with liver, phosphatidylcholine of unstimulated lymphocytes was found to contain relatively high amounts of palmitic acid in position 2 and oleic acid in position 1. After stimulation of rabbit thymus cells, the content of polyunsaturated fatty acids (linoleic and arachidonic acid) increased. Thus the ratio of polyenoic acids (18:2 + 20:4) to saturated fatty acids was doubled when compared to control cells. Similar results were obtained after in vivo stimualtion with Mycobacterium Calmette Guerin. The correlation of these findings with the activation of acyl-CoA:lysolecithin acyltransferase, and their relevance for changes of membrane fluidity during lymphocyte stimulation is discussed.

Animals↗
PubMed1975

Antibody-dependent cytotoxicity: modulation by the cytochalasins and microtubule-disruptive agents.

Cytochalasin B was shown to inhibit lysis of antibody-coated target cells by effector cells from rabbit spleen and lymph node. The inhibitory activity was dose-dependent and reversible. At low concentrations of cytochalasin B (0.15 to 0.3 mug/ml) enhancement of antibody-dependent cytotoxicity was observed. The drug appeared to act at an early stage of the lytic pathway after effector cell-target cell interaction, but before triggering of the cytotoxic event. Cytochalasin A was shown to be a more potent but similarly reversible inhibitor of antibody-dependent cytotoxicity. No enhancement of cytotoxicity was seen at non-inhibitory concentrations of cytochalasin A. The microtubule-disruptive agents colchicine (10-4 M), vinblastine (10-5 M) and colcemid (10-6 M) did not influence antibody-dependent cytotoxicity at concentrations which were not toxic to the effector cells. Our results suggest that antibody-dependent cytotoxicity is a surface membrane-initiated process and microtubule-associated functions are not essential.

Animals↗