bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of macrophage-mediated tumoricidal activity by neuropeptides and neurohormones.
Authors: Koff W C , Dunegan M A 
Published: January 2023

Abstract
Recent evidence has suggested that stress may suppress the immune system and increase the frequency and severity of viral and neoplastic disease. The mechanisms for stress-induced modulation of immune function are unclear, but several neuropeptides are thought to be involved. Because macrophages play an important role in the host defense against infection and neoplasia, several stress-related neuropeptides were screened in efforts to determine whether these substances affect macrophage-mediated tumoricidal activity. Adrenocorticotropin and noradrenaline each completely blocked the capacity of mouse recombinant interferon-gamma (INF-gamma) to activate murine peritoneal macrophages to a tumoricidal state as measured by the lysis of 125I-UdR-labeled melanoma target cells. Vasoactive intestinal peptide significantly potentiated the suppressive effects of noradrenaline. In contrast, neurotensin markedly enhanced the cytolytic capability of peritoneal macrophages activated with INF-gamma. Several other neuropeptides, including substance P, alpha-endorphin, beta-endorphin, Leu-enkephalin, and Met-enkephalin, had no effect on macrophage activation. These findings demonstrate that selected stress-related neuropeptides and neurohormones significantly modulate the capacity of macrophages to attain a tumoricidal state and suggest that alteration of macrophage function by neuropeptides may be a prominent feature of stress-induced enhancement of neoplastic disease.
E receptor-related immunosuppressive factor in malignant pleural fluid and plasma: molecular mechanism of action on DNA-polymerase-alpha.
Authors: Oh S K , Lapenson D P 
Published: January 2023

Abstract
We previously purified a potent serum suppressor factor from malignant ascites fluid and showed that it had serologic cross-reactivity with E receptor of human T lymphocytes. We termed this factor "suppressive E receptor factor" (SER). Subsequent studies on SER showed that SER interfered with the production of interleukin 1 and 2 as well as interfering with their activities on target cells. However, SER was not directly cytotoxic to lymphocytes. In this study, we compared the inhibitor of DNA-polymerase (IDP) activity with the suppressive activity on phytohemagglutinin-induced DNA synthesis on intact cells. These two activities were closely correlated (with a linear correlation coefficient of 0.988) even with the whole plasmas derived from cancer patients. Fractionation and purification of IDP activity identified it with SER of a similar potency. Therefore, SER appeared to exhibit its potent immunosuppressive effect via its direct interference on DNA-polymerase activity. Furthermore, the DNA-polymerase inhibitory activity of SER appeared to be specific to DNA and it did not affect the RNA-polymerase activity. SER inhibition of DNA polymerase activity with respect to DNA primer as well as with the nucleotide substrate. Direct inhibition on DNA-polymerase-alpha activity may be one of the possible mechanisms of action of SER on lymphocyte proliferation.
A role for helper cell subpopulations in a genetically controlled cytolytic T lymphocyte response to the H-2Db antigen.
Authors: French D L , Plate J M 
Published: January 2023

Abstract
The primary cytolytic T lymphocyte (CTL) response to the H-2Db antigen in several strain combinations appears to be under genetic control. Our studies were undertaken to determine the mechanisms involved in responders that were absent from the nonresponders and that led to CTL generation. In these studies, H-2Dk-anti-H-2Db combinations served as CTL responders, and H-2Dd-anti-H-2Db combinations served as CTL nonresponders. The nonresponsiveness of the H-2Dd-anti-H-2Db strain combinations appeared to be due to the inability of the Db antigen to activate a helper cell subpopulation. The activation of this helper cell subpopulation, as demonstrated in the H-2Dk-anti-H-2Db response, resulted in the production of factors that led to the induction of CTL differentiation. Antigen-specific pre-CTL for Db were present in the nonresponders as well as in the responders. Interleukin 2 (IL 2)-producing cells were also present in both nonresponders and responders, because all strain combinations tested in this system produced detectable levels of IL 2. Additional analysis of these data suggested that different determinants on the H-2Db antigen were recognized by distinct populations of cells. The activation of pre-CTL and IL 2-producing cells by the recognition of determinants on the H-2Db antigen was not sufficient for the generation of effector CTL, as demonstrated in the H-2Dd-anti-H-2Db response. We suggest that determinants on the H-2Db antigen that are distinct from those recognized by pre-CTL and IL 2-producing cells are recognized by a helper cell subpopulation in the H-2Dk strains, and that activation of this subpopulation is required for the production of factors that mediate CTL differentiation. This is the first description of the role that CTL differentiation factors play in a genetically controlled response.
Self-association of the seventh component of human complement (C7): dimerization and polymerization.
Authors: Pressner K T , Podack E R , Müller-Eberhard H J 
Published: January 2023

Abstract
Two association reactions of isolated C7 are described. The incubation of isolated C7 in 1% deoxycholate results in hemolytically inactive dimeric C7 that has a sedimentation coefficient of 7.3S. Dimeric C7 expressed hydrophobic domains that bound 41 +/- 4 mol deoxycholate per mol C7 and that aggregated upon removal of the detergent. The dimeric nature of the deoxycholate-treated C7 was demonstrated by analytical ultracentrifugation and by gel filtration, and yielded the following parameters: Mr = 230,000; diffusion coefficient, D = 2.9 X 10(-7) cm2/sec, and Stokes' radius, rH = 7.3 nm. Dimeric C7 exhibits an increased electrophoretic mobility and an increased beta-sheet structure, as compared with monomeric C7. Upon incubation with deoxycholate-phospholipid mixed micelles and removal of the detergent, the dimeric C7 became firmly associated with the lipid vesicles and was partially aggregated in the lipid bilayer. Trypsin treatment released approximately 50% of the protein material from the C7 vesicle complex. The other association reaction of isolated C7 occurs upon incubation with 1 M guanidine HC1; C7 forms soluble, linear protein polymers that have sedimentation coefficients ranging from 20 to 30S. The strands are 5 to 8 nm wide and vary in length between 20 to 100 nm. They tend not to aggregate, they are hemolytically inactive, and they exhibit increased beta-sheet structure, as compared with monomeric C7. They can be dissociated to hemolytically active monomers by exposure to 4 M guanidine HC1 and by subsequent 100-fold dilution with buffer. Isolated C5 or C6 did not exhibit any of these properties. The results suggest that the properties acquired by C7 in the hydrophilic-amphiphilic transition may be responsible for the expression of the membrane binding site of "metastable" C5b-7 and for the polymerization of C5b-7 within the target membrane.
Successful generation of cytotoxic T lymphocytes specific for self immunoglobulin-determinants on B lymphocytes.
Authors: Dohi Y , Higasa M , Nishimura M , Hirayama A , Takagaki Y , Yamada K , Inoue K , Shinka S 
Published: January 2023

Abstract
Cytotoxic T lymphocytes (CTL) specific for self immunoglobulin (Ig) determinants on B lymphocytes were successfully generated. These CTL were induced with stimulator B hybridoma cells bearing self Ig determinants in responders compatible with the stimulators in H-2 antigens but disparate in minor H antigens. Their specificities were directed toward the idiotype and probably the allotype structures of Ig receptors on stimulator B cells. However, no CTL specific for Ig structures other than the idiotype and the allotype were detected. These data indicate the presence of specific precursor CTL for self B cell clones and suggest the possible development and function of these CTL in certain situations.
Structural analysis of the epitope recognized by a monoclonal antibody directed against tricyclic antidepressants.
Authors: Marullo S , Hoebeke J , Guillet J G , Strosberg A D 
Published: January 2023

Abstract
After somatic cell fusion between splenocytes of immunized BALB/c mice and NS-1 myeloma cells, a clone was obtained that secreted an anti-nortriptyline antibody of the IgG1 kappa isotype. The association constant of this antibody for pharmacologically active tricyclic antidepressant drugs ranged from 0.6 X 10(7) to 3 X 10(7) M-1. From thermodynamic and binding studies as well as tridimensional structures of tested compounds, the epitope recognized by the monoclonal antibody appeared to include both a hydrophobic tricycle in which the two phenyl rings form an angle of 120 to 130 degrees, and a side chain in which the amino group is separated from the two lateral rings of the tricyclic structure by a distance of approximately 5.9 A and 7.5 A, respectively. This conformation seems to be the one interacting with muscarinic acetylcholine brain receptors.
Biochemical analysis of desensitization of mouse mast cells.
Authors: Ishizaka T , Sterk A R , Daeron M , Becker E L , Ishizaka K 
Published: January 2023

Abstract
Biochemical mechanisms of desensitization were explored by using peritoneal mouse mast cells saturated with monoclonal mouse IgE anti-DNP antibody. It was found that a 1-min incubation of the sensitized cells with 0.01 micrograms/ml DNP-HSA in the absence of Ca2+ was sufficient to desensitize the cells completely. The treated cells failed to release a detectable amount of histamine upon incubation with an optimal concentration (0.1 to 1.0 micrograms/ml) of DNP-HSA and Ca2+. Determination of the number of antigen molecules bound to mast cells revealed that only a small (less than 10%) fraction of cell-bound IgE antibody molecules reacted with desensitizing antigen, and that desensitized cells and untreated (sensitized) cells could bind comparable amounts of antigen upon incubation with rechallenging antigen. However, the binding of antigen molecules to desensitized cells failed to induce any of the early biochemical events, i.e., phospholipid methylation, cAMP rise, and 45Ca uptake, as well as histamine release. It was also found that intracellular cAMP levels in desensitized cells were comparable to those in sensitized cells. Desensitization by a suboptimal concentration of DNP-HSA was prevented by inhibitors of methyltransferases, such as 3-deaza adenosine plus L-homocysteine thiolactone. Sensitized cells pretreated with 0.01 micrograms/ml DNP-HSA in the absence of Ca2+ and in the presence of the methyltransferase inhibitors responded to an optimal concentration of antigen for histamine release when they were rechallenged in the presence of Ca2+. Inhibition of desensitization by methyltransferase inhibitors was reversed by the addition of S-adenosyl-L-methionine to the system. The results indicated that the activation of methyltransferases, induced by receptor bridging, is involved in the process of desensitization. Desensitization was inhibited by reversible inhibitors of serine proteases, such as p-aminobenzamidine, indole, and synthesized substrates of rat mast cell proteases. It was also found that diisopropylfluorophosphate (DFP), an irreversible inhibitor of serine proteases, completely blocked desensitization at the concentration of 10 to 40 nM. This concentration of DFP did not affect the antigen-induced histamine release, whereas 100- to 1000-fold higher concentrations of DFP did inhibit histamine release. The results suggest that serine proteases are involved in both the induction of histamine release and desensitization, and that the protease involved in desensitization is distinct from that involved in triggering histamine release.
Prostaglandin production by phagocytic cells of the mouse thymic reticulum in culture and its modulation by indomethacin and corticosteroids.
Authors: Homo-Delarche F , Duval D , Papiernik M 
Published: January 2023

Abstract
The production of prostaglandins by phagocytic cells of the thymic reticulum in culture (P-TR) was studied by using high pressure liquid chromatography and radioimmunoassay. Radioimmunologic determinations showed that thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1 alpha (6 keto-PGF1 alpha) were the major compounds released into the culture medium, whereas prostaglandin F2 alpha (PGF2 alpha) was only a minor component. Indomethacin and dexamethasone exerted a similar pattern of differential inhibition of the secretion of prostanoids. PGE2 and 6-keto PGF1 alpha productions were markedly decreased by these anti-inflammatory drugs, whereas those of TXB2 and PGF2 alpha were not or were only slightly affected. Experiments performed with an antiglucocorticoid compound (RU 38486) showed that the steroid-induced inhibition of prostanoid secretion is a classical receptor-mediated action. These results demonstrated that phagocytic cells of the thymic reticulum, which resemble the thymic interdigitating cells, produce several types of prostaglandins. Because it has been described that P-TR regulate thymocyte proliferation in vitro via the secretion of both interleukin 1 and PGE2, these results suggest that anti-inflammatory agents may be able to modulate the thymic microenvironment and, consequently, thymocyte proliferation.
Regulation of the Fc-receptor-mediated respiratory burst: treatment of primed murine peritoneal macrophages with lipopolysaccharide selectively inhibits H2O2 secretion stimulated by immune complexes.
Authors: Johnston P A , Adams D O , Hamilton T A 
Published: January 2023

Abstract
The effect of bacterial lipopolysaccharide on the Fc-receptor-mediated respiratory burst in murine peritoneal macrophages has been examined. After treatment overnight with small quantities of LPS, macrophages exhibited dramatic diminution of their capacity to generate and secrete H2O2 when triggered with immune complexes. The effect of LPS treatment was dependent on the state of macrophage functional activation; only cells that were primed or fully activated in vivo or were treated with interferon-gamma in vitro were sensitive to this effect of LPS. The LPS-mediated loss of secretory function was both dose and time dependent and could be reproduced with the lipid A moiety of LPS. The effect was selective for H2O2 secretion triggered through the Fc receptor; the respiratory burst stimulated by phorbol diesters remained unaltered. Furthermore, LPS treatment did not alter either binding or ingestion of radiolabeled immune complexes in parallel with the change in H2O2 secretion, indicating that the suppressive effect was not due to compromised endocytic function. These results indicate that LPS treatment of primed macrophages regulates the function of Fc receptors and may uncouple receptor occupancy from generation and secretion of H2O2.
Transduction by leukotriene B4 receptors of increases in cytosolic calcium in human polymorphonuclear leukocytes.
Authors: Goldman D W , Gifford L A , Olson D M , Goetzl E J 
Published: January 2023

Abstract
The uptake of Quin-2 by human polymorphonuclear (PMN) leukocytes permitted accurate fluorimetric quantification of the cytosolic concentration of intracellular calcium [( Ca+2]in), without altering the expression of the two subsets of leukotriene B4 (LTB4) receptors, as assessed by the binding of [3H]LTB4. Chemotactic concentrations of LTB4 elicited a rapid increase in [Ca+2]in, which reached a peak within 0.6 to 1 min and then decayed back to baseline levels by 6 to 10 min. The maximal increase and the half-maximal increase in [Ca+2]in were achieved by LTB4 at mean concentrations of 5 X 10(-10) M and 2 X 10(-10) M, respectively, where the binding of LTB4 to high-affinity receptors predominates. A rank order of potency of LTB4 greater than 5(S),12(S)-6-trans-LTB4 greater than 12(S)-LTB4 was established for the elicitation of increases in [Ca+2]in, which reflects the binding of the isomers to low-affinity receptors. PMN leukocytes were preincubated with 10(-8) M LTB4 to induce chemotactic deactivation, which eliminates the expression of high-affinity receptors without altering the expression of the low-affinity receptors for LTB4. LTB4 elicited an increase in [Ca+2]in in the deactivated PMN leukocytes with an EC50 of 3 X 10(-8) M, which is similar to the Kd for LTB4 binding to the low-affinity receptors. Two lines of cultured human leukemic cells, IM-9 and HL-60, did not bind LTB4 specifically and did not show any change in [Ca+2]in upon the addition of 3 X 10(-8) M LTB4. The HL-60 human promyelocytic leukemia cell line was induced to differentiate in 1% dimethyl sulfoxide to leukocytes with more mature myelocytic characteristics. Differentiated HL-60 cells expressed an average of 54,000 low-affinity receptors for LTB4 per cell with an average dissociation constant of 7.3 X 10(-8) M and concurrently developed the capacity to respond to LTB4 with an increase in [Ca+2]in. The binding of LTB4 to either high-affinity or low-affinity receptors appears to be sufficient to initiate an increase in [Ca+2]in in human PMN leukocytes and differentiated HL-60 cells. The specificity of LTB4 receptors in transducing maximum increases in [Ca+2]in is determined by the subset of receptors that predominate as a result of the concentration of LTB4 and the state of the responding cells.
Studies on the cytolytic attack mechanism of the cytotoxic T lymphocyte (CTL): preparation of antisera against cellfree cytosolic extracts of a CTL clone capable of blocking the lethal hit stage of CTL cytolysis and analysis of the cytolytic structure.
Authors: Hiserodt J C 
Published: January 2023

Abstract
Rat antiserum (as well as purified IgG and F(ab')2 fragments) raised against cellfree cytosolic extracts (CFE) of an alloimmune cytotoxic T lymphocyte (CTL) clone (B6.1.SF.1) is a potent inhibitor of CTL-mediated cytotoxicity. Inhibition by this antiserum (termed alpha CTLL) occurred during the postbinding lethal hit stages of cytolysis, because it did not inhibit target cell binding, nor did it prematurely dissociate CTL-target cell conjugates; inhibition was observed regardless of the H-2 haplotype of the target cell or CTL employed; inhibition was reversible when pretreated, and washed CTL were used as effectors; and in Ca++ pulse experiments alpha CTLL inhibited cytolysis beyond the Ca++-dependent (lethal hit) stage of cytolysis. This antiserum did not inhibit lysis of P815 cells by activated murine macrophages or by human cytotoxic cells, and extensive absorption of the antiserum on viable thymocytes, normal spleen cells, or CTL did not reduce its blocking activity. CFE prepared from several sources of CTL, including in vivo elicited peritoneal exudate lymphocytes (PEL), secondary MLC-generated CTL, alloimmune splenic T cells, and CTL clones, contained material(s) that inhibited the ability of alpha CTLL to block CTL-mediated cytolysis. The inhibitory activity was not detected in CFE from a variety of noncytotoxic cell sources, including thymocytes, normal C57BL/6 spleen cells, EL4 or P815 tumor cells, macrophages, and helper T cell clones. It was also absent in CFE prepared from human CTL cells. Furthermore, although alpha CTLL neutralizing activity was not detectable in CFE prepared from memory CTL, it rapidly appeared in CTL parallel to the development of cytolytic activity during secondary MLC cultures. The inhibitory material in CTL-CFE appeared to be specific for alpha CTLL antibody, as it did not affect the CTL blocking activity of anti-Lyt-2 or anti-target cell antisera. Finally, CTL-CFE did not contain proteases that degraded the alpha CTLL antibody. By the use of a soluble-phase immunoabsorbent assay, the biochemical properties of materials present CFE derived from CTL and reactive with alpha CTLL antibody were examined. CTL cytosolic material(s) reactive with alpha CTLL IgG was unstable to brief heating (50 degrees C) or acidic pH, but not to high ionic strength buffers. The material was inactivated by treatment with pronase but not by DNase, collagenase, or trypsin. Gel filtration chromatography of CTL-CFE revealed multiple peaks of alpha CTLL neutralizing activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of sodium on chemotactic peptide binding to polymorphonuclear leukocytes.
Authors: Zigmond S H , Woodworth A , Daukas G 
Published: January 2023

Abstract
The affinity of binding of the chemotactic peptide N-formylnorleucylleucylphenylalanine to rabbit peritoneal polymorphonuclear leukocytes is increased when sodium ions are removed from the medium. In Hanks' balanced salt solution, the dissociation constant of the binding is about 2 X 10(-8) M, while in Na+-free medium, the dissociation constant is between 3 and 6 X 10(-9) M. Removal of Na+ appears to cause little or no change in receptor number. The change in affinity is rapid and reversible, occurs at 4 degrees C as well as 37 degrees C, and occurs when the Na+ is replaced by K+, choline, or sucrose. The increased binding of low concentrations of peptide is seen on broken as well as whole cells and therefore does not depend on an ion gradient across the membrane. The high affinity receptors are functional in mediating peptide uptake and lysosomal enzyme release. The receptors undergo down-regulation in Na+-free medium, and the dose dependence of the receptor loss is shifted to lower concentrations consistent with the higher affinity of the binding.
Induction of granuloma modulation in murine schistosomiasis mansoni by enteric exposure to schistosome eggs.
Authors: Weinstock J V , Blum A M , Kassab J T 
Published: January 2023

Abstract
Enteric administration of antigen can induce systemic tolerance. In murine schistosomiasis mansoni, blood flukes produce eggs which enter the intestine. An immunologic phenomenon associated with this disease is a spontaneous diminution in the intensity of the granulomatous response in the liver, lungs, and colonic mucosa with chronic infection, which is termed modulation. It was determined whether modulation of liver granulomas could be induced by enteric immunization with schistosome eggs. Mice infected for 4 wk were immunized by injection of 25,000 eggs into cecal pouches. This induced modulation of liver granulomas by the eighth week of infection. Neither cecal injection of normal saline nor i.p. or subcutaneous injection of eggs could induce the modulatory process. Modulation could be adoptively transferred from enterically immunized donors by injection of spleen cells into infected recipients or into uninfected recipients with synchronous liver granulomas induced by the hepatic embolization of schistosome eggs. Spleen cells treated with anti-Thy-1.2 or anti-Lyt-1.1 and complement could no longer adoptively transfer modulation. These data show that enteric immunization with schistosome eggs can induce modulation of the liver granuloma by a cellular mechanism similar to that described for the natural infection.