bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biphasic platelet-activating factor synthesis by human monocytes stimulated with IL-1-beta, tumor necrosis factor, or IFN-gamma.
Authors: Valone F H , Epstein L B 
Published: December 2022

Abstract
The capacity of IL-1-beta, TNF, and IFN-gamma to stimulate platelet-activating factor (PAF) synthesis by human monocytes is examined in our report. All three cytokines induced PAF synthesis in a novel biphasic pattern with peaks of PAF synthesis 1 to 2 and 6 to 8 h after stimulation of the monocytes. In contrast, calcium ionophore A23187 elicited a single peak of early PAF synthesis. PAF in the early peak was largely retained intracellularly whereas PAF in the late peak was largely released into culture fluids. Combinations of cytokines were subadditive or antagonistic in inducing PAF synthesis. Cycloheximide inhibited the late peak of PAF synthesis indicating that protein synthesis is required for synthesis of the phospholipid PAF. Specific antibodies to TNF or IL-1-beta inhibited the late peak of PAF synthesis induced by IFN-gamma indicating that late PAF synthesis is dependent on cytokine synthesis. The quantities of PAF produced by cytokine-activated monocytes are sufficient to activate human monocytes. Thus, these studies suggest that PAF may mediate in part monocyte activation by cytokines.
Cloning and high level expression of a chimeric antibody with specificity for human carcinoembryonic antigen.
Authors: Beidler C B , Ludwig J R , Cardenas J , Phelps J , Papworth C G , Melcher E , Sierzega M , Myers L J , Unger B W , Fisher M 
Published: December 2022

Abstract
A mouse/human chimeric antibody has been constructed by using variable light and variable heavy regions from a murine hybridoma specific for human carcinoembryonic antigen (CEA) (CEM231.6.7). These V regions were combined with kappa and gamma-1 constant region genes cloned from human lymphocytes. The chimeric constructs were sequentially electroporated into murine non-Ig-producing myeloma (P3.653) and hybridoma (SP2/0) cell. Significant differences were seen in expression levels between the two cell types. High levels of expression (24 to 32 micrograms/ml/10(6) cells) were seen with several of the anti-CEA SP2/0 transfectomas but not with the P3.653 cells. The SP2/0 transfectoma lines were adapted to serum-free, chemically defined media and grown in large scale fermentation cultures where they continued to secrete high levels of antibody. The chimeric antibodies remain reactive against human CEA with affinity constants comparable to that of the parental hybridoma antibody. High level expression will make practical the production of chimeric antibodies for in vivo therapeutic and diagnostic purposes.
Anti-idiotypic antibodies against UV-induced tumor-specific CTL clones. Preparation in syngeneic combination.
Authors: Kuribayashi K , Tanaka C , Matsubayashi Y , Masuda T , Udono H , Abe M , Nakayama E , Shiku H 
Published: December 2022

Abstract
In this study, we first established several CTL clones of (BALB/c x C57BL/6)F1 origin that were specific for either syngeneic UV female 1 or UV male 1 fibrosarcoma cell lines. All the CTL clones had Thy-1+ Lyt-2+ L3T4- phenotypes and showed Kd restriction when lysing the corresponding target cells. Sera obtained from syngeneic animals immunized with three CTL clones, 10B-5 for UV female 1, and CTL9 and CTL10 for UV male 1, showed specific inhibition of target cell lysis with the corresponding CTL clones. The inhibitory activities were found in sera of the majority of immunized animals. Because the inhibitory activity resides in protein A-binding fraction, mAb were produced by hybridizing spleen cells of hyperimmune animals. N1-56 was thus obtained from a mouse immunized with 10B-5 CTL clone reactive with UV female 1. N1-56 was clonotype specific, reacting with 10B-5 but not with other CTL lines or leukemia cell lines. No N1-56+ cells were detectable in thymocytes, lymph node cells, or spleen cells of either naive or UV female 1-immune CB6F1 mice. Immunoprecipitation showed that N1-56 reacts with 90,000 Mr molecules on 10B-5 CTL clone under nonreducing conditions and 45,000 Mr molecules under reducing conditions, indicating its reactivities with idiotypic determinants of TCR on the CTL clone. N1-56 inhibited lytic activity of 10B-5, but neither N1-56 nor alpha-10B-5 hyperimmune serum inhibited that of alpha-UV female 1 mixed lymphocyte tumor cell culture cells. N1-56 induced proliferation of 10B-5 without addition of Ag.
Quantitative analyses of the relationship between C3 consumption, C3b capture, and immune adherence of complement-fixing antibody/DNA immune complexes.
Authors: Edberg J C , Tosic L , Wright E L , Sutherland W M , Taylor R P 
Published: December 2022

Abstract
We have studied the turnover of the third component of C (C3) and capture of the major cleavage fragment of C3 produced during C activation (C3b) that occurs when soluble antibody/DNA immune complexes (IC) active C. We used the Amersham RIA kit for the minor cleavage fragment of C3 produced during C activation (C3a), and a new assay utilizing mAb to C3b to measure the fraction of active C3 in a C source after the IC activate C. These mAb, along with a mAb to human IgG, allowed us to measure IC stoichiometries. The efficiency of C3 turnover by the IC is quite high, and under conditions of Ab excess, the maximum number of IgG bound per dsDNA corresponds to 1 IgG/20 to 30 base pairs. The maximum number of C3b found in the IC corresponds to less than 1 C3b/IgG, and the vast majority of the captured C3b is bound to the IgG, and not to the DNA. We identified several IC that consumed large amounts of C3, and captured large amounts of C3b, but did not bind to human E via C3b receptors (C receptor type 1). This finding suggests that the ability of IC to bind to human E depends upon the number and distribution of captured C3b molecules and the conformation and size of the DNA Ag, which reflects the need for multivalent binding between several properly arrayed C3b and a "cluster" of C receptor type 1 on the human E membrane. IC that activate C3 but do not bind to E would presumably "escape" the E IC clearance mechanism, but could deposit in susceptible organs and tissues and play a role in the pathogenesis of SLE because of their potential to generate the inflammatory products of C activation.
Characterization of a cell surface-expressed disulfide-linked dimer involved in murine T cell activation.
Authors: Yokoyama W M , Koning F , Kehn P J , Pereira G M , Stingl G , Coligan J E , Shevach E M 
Published: December 2022

Abstract
We have produced a hamster mAb, H1.2F3, which was derived by immunization with a murine TCR-gamma delta + epidermal T cell line. H1.2F3 immunoprecipitates a cell surface-expressed disulfide-linked dimer that has a m.w. of 85,000 under non-reducing conditions and consists of subunits of 35,000 to 39,000 m.w. This dimer is distinct from the CD3-associated TCR-gamma delta complex (CD3/TCR), inasmuch as H1.2F3 does not co-precipitate or co-modulate with the CD3/TCR complex and recognizes an Ag with a single-peptide backbone of 22,000 m.w. after N-Glycanase treatment. H1.2F3 is weakly reactive with a small percentage of cells from unfractionated thymus, spleen, or lymph node, but reactivity with both T and B lymphocytes is markedly enhanced by a brief period of stimulation with Con A or PMA in vitro. This enhancement requires de novo protein synthesis. Enhanced expression of the H1.2F3 Ag can also be induced in vivo by injection of Con A or anti-CD3. H1.2F3 is a potent stimulator of T, but not B, cell proliferation in the presence of PMA and FcR-bearing accessory cells. These functional and biochemical studies strongly suggest that the Ag recognized by H1.2F3 is the murine homologue of the human CD28 Ag recognized by mAb 9.3.
IL-4/B cell stimulatory factor 1 stimulates T cell growth by an IL-2-independent mechanism.
Authors: Brown M , Hu-Li J , Paul W E 
Published: December 2022

Abstract
Resting T cells are stimulated to synthesize DNA by IL-4 and phorbol myristate acetate (PMA). This response of T cells to IL-4 plus PMA is independent of the action of IL-2 as judged by 1) the lack of IL-2 in supernatants of stimulated cells, 2) the failure to detect IL-2 mRNA in stimulated cells by in situ hybridization, 3) the inability of anti-IL-2R antibody and of anti-IL-2 antibody to block responses to IL-4 plus PMA, and 4) the failure of cyclosporin A to block responses. T cells also respond to anti-CD3 antibodies and IL-4 in the presence of anti-IL-2R antibodies. IL-4 stimulation of growth of the long term T cell line HT-2 also appears to be independent of the action of IL-2. No IL-2 mRNA is found in IL-4-stimulated HT-2 cells by Northern blotting; the response of HT-2 cells to IL-4 is not blocked by anti-IL-2R antibodies; the response of HT-2 cells to IL-4 is not inhibited by cyclosporin A. Although IL-4 stimulation of T cells is independent of IL-2, IL-4 plus PMA treatment of resting T cells does cause enhanced expression of IL-2R and prepares cells to proliferate to IL-2 alone. In both these properties IL-4 resembles IL-2. These experiments lead us to conclude that IL-4 can act as an alternative to IL-2 as authentic T cell growth factor.
Induction of monocyte migration by recombinant macrophage colony-stimulating factor.
Authors: Wang J M , Griffin J D , Rambaldi A , Chen Z G , Mantovani A 
Published: December 2022

Abstract
Human recombinant macrophage-CSF (M-CSF) induced migration across polycarbonate or nitrocellulose filters of human peripheral blood monocytes. Checkerboard analysis of M-CSF-induced migration, performed by seeding different cytokine concentrations above and below the filter, revealed that the locomotory response involved chemotaxis, though some gradient-independent augmentation of migration occurred. Polymixin B did not affect M-CSF chemotaxis and M-CSF was active on monocytes from the LPS-unresponsive mouse strain C3H/HeJ. These findings rule out a contribution of minute endotoxin contamination, below the sensitivity of the Limulus assay, in M-CSF chemotaxis. Rabbit anti-M-CSF antibodies inhibited the chemotactic activity of recombinant M-CSF, thus further indicating that the M-CSF molecule was indeed responsible for chemotaxis. M-CSF preparations encoded by 224 or 522 amino acid cDNA clones were equally effective in inducing monocyte migration. Recombinant M-CSF did not elicit a migratory response in large granular lymphocytes and in endothelial cells under conditions in which appropriate reference attractants were active. A modest stimulation of migration of polymorphonuclear leukocytes, inhibitable by antibodies, was observed at high cytokine concentrations (10 to 100 times higher than those required for monocyte locomotion). The maximal polymorphonuclear leukocytes response evoked by M-CSF was small compared to that evoked by reference chemoattractants or to that evoked by the same cytokine in monocytes. Hence, M-CSF is a potent chemoattractant for mononuclear phagocytes and exerts its action preferentially on cells of the monocyte-macrophage lineage. M-CSF, produced locally by activated macrophages, may play a role in the selective recruitment from the blood compartment of mononuclear phagocytes to amplify resistance against certain noxious agents.
Tumor necrosis factor-induced activation of peritoneal macrophages is regulated by prostaglandin E2 and cAMP.
Authors: Lehmmann V , Benninghoff B , Dröge W 
Published: December 2022

Abstract
Human rTNF-alpha stimulates the metabolism of murine peritoneal macrophages as demonstrated by an increased consumption of arginine and an increased release of L-ornithine. This TNF-mediated effect is augmented by several substances that raise the intracellular concentration of cAMP, including PGE2, cholera toxin, and dibutyryl-cAMP. TNF also stimulates the endogenous production of PGE2 in cultures of peritoneal macrophages. The addition of the cyclo-oxygenase inhibitor, indomethacin, suppresses the TNF-mediated metabolic activation of macrophages, and this suppressive effect of indomethacin is overcome if exogenous PGE2 or cholera toxin is added to the culture. Taken together, the experiments indicate that the TNF-induced production of PGE2 and the PGE2-induced increase of the intracellular cAMP concentration are essential elements of an auto-regulatory loop that controls the magnitude of the TNF-mediated effect in the macrophage.
Allogeneic manipulation of the GAT idiotypic cascade. Immunization of C57BL/6 mice by BALB/c anti-idiotypes stimulates similar strain-specific V genes as the original antigen.
Authors: Corbet S , Hirn M , Roth C , Theze J , Fougereau M , Schiff C 
Published: December 2022

Abstract
Antibodies specific for the immunizing Ag (Ab1) (Id+ Ag+) and Ab3 (Id+ Ag+ or Id+ Ag-) of the (Glu60 Tyr10 Ala30) (GAT) idiotypic cascade express similar pGAT public determinants in BALB/c and C57BL/6 strains. These determinants have been shown to be dependent upon both VH and Vkappa encoded segments. The VH of the BALB/c Ab1 (germ-line gene H10) and that of the C57BL/6 Ab1 (germ-line gene V186-2) are only 75% homologous, whereas VK are much more conserved. C57BL/6 mice were immunized with BALB/c Ab2 (anti-idiotypic) antibodies and monoclonal Ab3 were derived after fusion of immunized spleen cells with the nonsecreting hybridoma cell line Sp/2.0-Ag. From 13 cell lines, five clones (four Id+ Ag- and one Id+ Ag+) were isolated and the mRNA V regions sequenced. Immunization with BALB/c anti-idiotypes elicits expression of the same or closely related C57BL/6 VH and Vkappa genes as when C57BL/6 mice were immunized with GAT, although functional VH BALB/c equivalents have been isolated in the B6 strain. Our results suggest that manipulation of the repertoire via antigenic or idiotypic stimulation both lead to the expression of different genes in different strains. They further confirm that the immune system is largely degenerate, for both idiotype expression and Ag recognition.
Cell-mediated and glucocorticoid-mediated target cell lysis do not appear to share common pathways.
Authors: Dennert G , Landon C , Nowicki M 
Published: December 2022

Abstract
Target cell lysis by cytolyic lymphocytes follows a sequence of events that culminate in osmotic destruction of the target. Although it is clear that killer cell derived components play a crucial role in target cell lysis it is not clear to what extent the target itself is involved in its destruction. Recent observations have pointed to the possibility that glucocorticoid mediated and cell mediated lysis may utilize common pathways of cell lysis. In analyzing this question we found that cell lines that have nonfunctional glucocorticoid receptors like S49-78 and S49-88 are good targets for both NK and thymus-derived killer (TK) cells. Cell lines that are glucocorticoid sensitive such as Q1(4)6 are sensitive to NK-mediated lysis as its derivative HL4-6-3 which contains glucocorticoid receptors but is glucocorticoid resistant. An intriguing exception to this is the glucocorticoid-resistant mutant S49-4RD which is relatively resistant to both NK and TK lysis compared with parent S49. The resistance of S49-4RD to cell-mediated lysis we show here is most likely due to a defect in the target which results in its failure to trigger the cytolytic machinery in the killer cell rather than in its resistance to lysis per se. In support of this we demonstrate that lysis of S49-4RD by cytolytic granules from TK cells is normal. Moreover TK cells lyse S49-4RD as efficiently as its parent in the presence of the lectin Con A. The conclusion that S49-4RD has a defect in its ability to induce killer cells to initiate the cytolytic reaction is also in agreement with the finding that TK-S49-4RD conjugates show inefficient reorientation of the Golgi apparatus in the effector.
Protective role of IgE in immunocompromised rat toxoplasmosis.
Authors: Ridel P R , Auriault C , Darcy F , Pierce R J , Leite P , Santoro F , Neyrinck J L , Kusnierz J P , Capron A 
Published: December 2022

Abstract
In contrast to euthymic adult Fischer rats, immunocompromised Nu/Nu animals develop a lethal infection when inoculated with the RH strain of the protozoan Toxoplasma gondii. However, a significant period of survival is obtained when Nu/Nu rats are passively transferred with sera from 28-day infected Fischer +/+ (euthymic) animals. Specific IgE are involved since IgE-depleted sera are unable to afford such a protection. Only excreted/secreted Ag or living tachyzoites are able to induce a significant protective IgE response in intact animals. In addition, platelets or, to a lesser extent, eosinophil-rich populations from Toxoplasma infected or excreted-secreted Ag-immunized euthymic animals bear surface IgE and are cytotoxic for the parasite in vitro. Also, adoptive transfer of immune platelets confers a significant degree of protection to Toxoplasma-infected Nu/Nu animals. Our results clearly show the key role of Ag present in both living parasites and excreted-secreted Ag to induce, in this model, a protective IgE response. In addition, as in other parasitic infections, platelets and probably eosinophils are the effector cells involved in controlling parasitic dissemination during Toxoplasma infection in immunocompromised rats.
Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi. III. Genetic restriction and further characterization.
Authors: Gao X M , Schmidt J A , Liew F Y 
Published: December 2022

Abstract
Earlier papers in this series reported that the culture supernatant of splenic L3T4+, Lyt-2- T cells from susceptible CBA mice chronically infected with Trypanosoma cruzi contain a SS3 that can inhibit the induction of delayed-type hypersensitivity to a wide range of Ag. The SS is a glycoprotein with an apparent molecular mass of 30 to 60 kDa and is distinct from T. cruzi Ag, IL-1, IL-2, IL-3 or IFN-gamma. It also has no effect on Th cells for antibody, cytotoxic T cells or immediate-type hypersensitivity. In this paper, we report that SS can suppress the induction of proliferating T cells but not the presentation of Ag to a cloned T cell line (D10). It also has no effect on the induction of delayed-type hypersensitivity in vitro. SS is produced by a number of inbred mouse strains irrespective of their susceptibility to infection with T. cruzi (BALB/c, highly susceptible; CBA, susceptible; C57BL/10, resistant) but only CBA mice are sensitive to the suppressive action of SS. This is so whether the SS is derived from CBA, BALB/c, or C57BL/10. The sensitivity to SS is not a feature of the H-2k haplotype inasmuch as B10.BR and BALB/k mice (also H-2k) do not respond to SS. Attempts to purify SS with a range of biochemical techniques substantially enriched the specific activity but failed to produce a substance visualizable by analytical gel electrophoresis. IEF chromatography revealed SS activity spanning a pH range from 6 to less than 4. This suggests that SS is likely to be a minor heterogeneous component of the suppressive supernatant. The genetically highly restricted nature of its action is intriguing and may explain some of the contradictory reports in the literature on this subject.
Adoptively transferred experimental autoimmune encephalomyelitis in SJL/J, PL/J, and (SJL/J x PL/J)F1 mice. Influence of I-A haplotype on encephalitogenic epitope of myelin basic protein.
Authors: McCarron R , McFarlin D E 
Published: December 2022

Abstract
Guinea pig basic protein (GPBP)-immune lymph node cells (LNC) from SJL, PL, and SJL x PL (F1) mice proliferated to whole GPBP and GPBP fragments 1-37, 43-88, and 89-169. All three strains of mice developed experimental allergic encephalomyelitis (EAE) by active immunization with whole GPBP or by passive transfer of LNC cultured with whole GPBP. SJL (H-2s) and PL (H-2u) mice developed EAE by active immunization with fragments 89-169 or 1-37, respectively, or by passive transfer of LNC cultured with the same Ag. F1 mice developed EAE by active immunization only with fragment 1-37 or by passive transfer of LNC cultured with either of the above fragments. Removal of macrophages (MO) from immune-F1 LNC resulted in the loss of a proliferative response and the ability to transfer EAE. Reconstitution of MO-depleted immune F1 T cells with either F1-, SJL-, or PL-MO restored the proliferative responses to whole GPBP and the three fragments. Cultures of immune F1 T cells reconstituted with any of the three MO populations and incubated with whole GPBP passively transferred EAE into naive F1 mice. Immune F1 T cells cultured with F1 MO in the presence of either fragment 1-37 or 89-169 transferred EAE. F1 T cells cultured with SJL MO were able to transfer EAE only if the Ag was fragment 89-169, whereas F1 T cells cultured with PL MO were able to transfer disease only if incubated in the presence of fragment 1-37. F1 mice are passively susceptible to EAE induced by adoptive transfer of cells reactive to either the N-terminal or C-terminal fragment and that the encephalitogenic determinant of GPBP is related to the genome of MO present in vitro.
Mitochondrial iron loss from leukemia cells injured by macrophages. A possible mechanism for electron transport chain defects.
Authors: Wharton M , Granger D L , Durack D T 
Published: December 2022

Abstract
Activated macrophages inhibit replication of murine lymphoblastic leukemia L1210 cells without lysis. This inhibition of replication is associated with abnormalities of mitochondrial electron transport at the level of NADH dehydrogenase (NADH-DH) and succinate dehydrogenase (SDH). The mechanism of inhibition is unknown, although it has been demonstrated that as NADH-DH and SDH activity is lost, iron is released from cells. Because both NADH-DH and SDH contain numerous iron-sulfur clusters, damage to these structures may be one result of injury by activated macrophages. L1210 cells were labeled with 55Fe and co-cultivated with activated murine peritoneal macrophages (injured L1210 cells). At 48 h, injured L1210 cells had released 83 +/- 8% (mean +/- SEM of 55Fe activity into the media, compared with 25 +/- 4% release from control and 37 +/- 7% from nondividing mitomycin C-treated control cells. All cells were greater than 90% viable. These differences were also reflected in the iron content of the cells. Mitochondria were then separated by centrifugation after cell disruption and 55Fe activity was found to be similarly decreased in both mitochondrial and nonmitochondrial fractions of injured L1210 cells. To further characterize the changes in mitochondrial iron content, mitochondrial proteins from injured and control L1210 cells were separated by IEF and 55Fe activity of gel slices was determined. There was selective loss of 55Fe activity in the area of the gel corresponding to SDH and NADH-DH, suggesting that iron loss from iron-sulfur clusters may occur in L1210 cells injured by activated macrophages. Iron uptake into L1210 cells after removal from macrophages showed a rapid large influx of radioactive iron. L1210 cells in contact with macrophages appear to develop an iron-depleted state, which is dependent on the continued presence of macrophages.