bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manipulation of the acute inflammatory response by dietary polyunsaturated fatty acid modulation.
Authors: Lefkowith J B , Morrison A , Lee V , Rogers M 
Published: December 2022

Abstract
Dietary polyunsaturated fatty acid modulation has been used as an anti-inflammatory strategy in experimental models of disease as well as in clinical trials. To elucidate the mechanisms underlying the anti-inflammatory effects of manipulating dietary polyunsaturated fatty acids, the in vivo effects of essential fatty acid (EFA) deficiency and (n-3) fatty acid supplementation were contrasted using a model of acute inflammation induced by the i.p. injection of zymosan into mice. Both diets led to a substantial decrease in tissue (n-6) fatty acid content. EFA deficiency was also characterized by the accumulation of (n-9) fatty acids, particularly 20:3 (n-9), the fatty acid that uniquely characterizes the deficiency state. Dietary (n-3) fatty acid supplementation led instead to marked increases in (n-3) fatty acids, especially 20:5 (n-3). With respect to the antiinflammatory effects of the two diets, EFA deficiency, but not (n-3) fatty acid supplementation, depleted levels of resident peritoneal macrophages. EFA deficiency was also more effective than (n-3) fatty acid supplementation in inhibiting the influx of polymorphonuclear neutrophils in response to zymosan. The effect of the two diets on the in vivo generation of leukotriene(LT)B also differed markedly. EFA deficiency completely inhibited the synthesis of LTB. Dietary (n-3) fatty acid supplementation, in contrast, reduced the production of LTB4 by only 50%. With (n-3) fatty acid supplementation LTB5 was produced. The more modest effect of (n-3) fatty acid supplementation in decreasing LTB4 generation was not due to blockade of the cyclooxygenase pathway. EFA deficiency, but not (n-3) fatty acid supplementation, was associated with the decreased synthesis of thromboxane. Although dietary fatty acid modulation has been shown to diminish platelet activating factor (PAF) synthesis, studies using the PAF receptor blocker, L659989, established that PAF was not a significant factor in the elicitation of leukocytes in this model of inflammation. In summary, the anti-inflammatory effect of EFA deficiency was more marked that that of dietary (n-3) fatty acid supplementation in acute inflammation. This difference in anti-inflammatory potential appeared to be due to either the greater effect of EFA deficiency in decreasing levels of resident peritoneal macrophages or in suppressing the in vivo generation of LTB4.
Long-term survival of adoptively transferred tumor-infiltrating lymphocytes in mice.
Authors: Alexander R B , Rosenberg S A 
Published: December 2022

Abstract
We examined the long term survival of adoptively transferred, cultured tumor-infiltrating lymphocytes (TIL) in sublethally irradiated nontumor-bearing mice. TIL were produced by culturing Thy-1-enriched single cell suspensions from a variety of murine tumors in exogenous IL-2 along with irradiated tumor cells and splenocytes. TIL were adoptively transferred i.v. to mice and such animals demonstrated a statistically significant degree of protection from a subsequent i.v. tumor challenge. This protection lasted up to 6 wk and occurred in the absence of exogenous IL-2 administration in vivo. Using congenic B6.PL Thy-1 alpha/CY mice we demonstrated directly that TIL can survive in vivo for up to 6 wk and that the adoptively transferred TIL were the source of the relative immunity to subsequent tumor challenge. We conclude that TIL contain cells with substantial functional longevity in vivo even in the absence of exogenous IL-2. These studies are relevant to ongoing clinical trials of TIL as a therapy for patients with advanced cancer.
Differences in turnover between thymic medullary dendritic cells and a subset of cortical macrophages.
Authors: Kampinga J , Nieuwenhuis P , Roser B , Aspinall R 
Published: December 2022

Abstract
To investigate the turnover of thymic accessory cells, we performed vascular thymus transplantation in RT7 congenic rats. mAb specific for one of the two allelic variants of the RT7 molecule, as well as mAb specific for either medullary interdigitating cells or a subset of cortical macrophages (M phi), were used on cryostat sections and cell suspensions prepared from grafted thymuses to monitor the turnover of these two cell types. In contrast to the complete turnover of interdigitating cells within 3 wk after transplantation, ED2-labeled cortical M phi showed a very slow turnover. Seventy-six days after transplantation, more than 30% of these M phi were found to be still of donor origin. The different turnover rates of these thymic accessory cells could reflect their function in T cell development.
Human T cell activation. Synergy between CD73 (ecto-5'-nucleotidase) and signals delivered through CD3 and CD2 molecules.
Authors: Massaia M , Perrin L , Bianchi A , Ruedi J , Attisano C , Altieri D , Rijkers G T , Thompson L F 
Published: December 2022

Abstract
Interaction of the glycosyl phosphatidylinositol-linked differentiation Ag CD73 (ecto-5'-nucleotidase) with the CD73-specific mAb 1E9 generates agonistic signals that strongly synergize with T cell activation induced by CD3 and CD2 mAb. This synergy is observed only when 1E9 is immobilized on plastic and occurs in the absence of accessory cells or exogenous lymphokines. 1E9 induces a rapid (though transient) increase in [Ca2+]i in a minor proportion (20 to 30%) of unfractionated T lymphocytes (presumably CD73+ cells). However, this [Ca2+]i mobilization is not sufficient to fully activate CD73+ T cells, as shown by the requirement of additional signals such as CD3 or CD2 stimulation to initiate T cell proliferation. These signals cannot be substituted by the exogenous lymphokines, rIL-1, rIL-2, or rIL-4, or PMA (when T cells are rigorously depleted of monocytes). These data indicate that CD73 may behave as an accessory molecule regulating interactions between T cells and antigens or APC. A comparison was carried out with mAb 9.3 to the differentiation Ag CD28, another agonistic molecule with activating properties similar to CD73. Despite their lower percentage, the ability of CD73+ T cells to amplify the proliferation induced by CD3 or CD2 mAb was equivalent or even greater than that of CD28+ T cells. Once activated, CD73+ cells may recruit the remaining (CD73-) cells primed by CD3 or CD2 stimulation. Based on these data, we suggest that CD73+ T lymphocytes may be a specialized subset to amplify immune responses originated by the CD3 and CD2 activation pathways. Finally, the functional association between CD73 and integral membrane molecules like CD3 and CD2 suggests that GPI-anchored molecules may play a role in transmembrane signaling mediated by conventional second messenger systems.
Phenotypic features and proliferative activity of B cell progenitors in X-linked agammaglobulinemia.
Authors: Campana D , Farrant J , Inamdar N , Webster A D , Janossy G 
Published: December 2022

Abstract
In this study, we applied mAb and heterologous antisera in double marker combinations to investigate the phenotype and the proliferative activity of immature B lineage cells in XLA. Bone marrow (BM) samples from eight male adult patients with no circulating B lymphocytes were studied. The proportions and the phenotype of the earliest identifiable B cell progenitors, expressing nuclear terminal deoxynucleotidyl transferase (TdT), cytoplasmic CD22, and membrane CD19 and CD10 were identical to those observed in normal BM. In XLA these cells represented 1.2% to 22% of BM mononuclear cells; 5% to 42% and 1% to 45% of such cells weakly expressed CD20 and CD37, respectively, and invariably lacked CD13 and CD33. Cytoplasmic mu+ sIg- pre-B cells were seen in low numbers (0.1% to 0.3%) in four samples and were undetectable in the remaining four. Consequently, the ratio TdT+/c mu+ was greater than 100 in five out of eight samples studied in contrast to the less than 10 values seen in normal individuals. The proliferative activity of B lineage progenitor cells was studied by using Ki67 and anti-bromodeoxyuridine mAb. Although the proliferation of TdT+ cells in XLA was comparable with that seen in normal BM samples (24% to 59% of TdT+ were Ki67+ and 11% to 27% incorporated bromodeoxyuridine), this was dramatically reduced in the c mu+ cells (no c mu+, Ki67+ seen in three samples where pre-B cells were observed). Thus, the abnormalities of B cell differentiation in XLA are first seen at the c mu+ pre-B stage and suggest a maturation block in the transition between TdT+, c mu- pre-pre-B cells and c mu+ pre-B cells. The severity of this block may be variable, allowing the generation of a near normal number of pre-B cells in some patients, which nevertheless have a defective proliferative activity. Finally, our study further supports the concept that the effects of the "XLA gene" are confined within the B lineage by demonstrating that the proportions of T cells bearing TCR-alpha beta and TCR-gamma delta in XLA are similar to those seen in normal individuals.
C1q receptor on murine cells.
Authors: Erdei A 
Published: December 2022

Abstract
Different cells and cell lines of murine origin were tested for their capacity to bind the C subcomponent C1q by using biotinylated human C1q and streptavidin-FITC. Cytofluorometric analysis of splenocytes and thymocytes shows that the majority of C1q-reactive cells reside in the population of B cells and macrophages. There is a significant difference in the C1q-binding capacity of in vitro activated cells; although more than half of the B cell blasts bind the C subcomponent, T cell blasts are virtually negative. It is shown that pre-B lymphomas and cell lines of myeloid origin bind C1q strongly (90 to 98%), whereas in the case of mature B cell lymphomas, plasmocytomas, and the tested T cell lines, the percentage of C1q binding cells varies from 0 to 56. C1q affinity chromatography of the detergent extracts from P388D1 and WEHI-3 cells followed by SDS-PAGE of the eluted proteins under reducing conditions reveals a band at approximately 80 kDa. Analysis of splenocytes shows two additional minor C1q-binding molecules with apparent molecular masses of 50 and 45 kDa, whereas in the case of B cell blasts three bands of similar density are seen at approximately 95, 50 and 45 kDa. C1q-receptors of murine cells are shown to be antigenically related to their human counterpart, because a polyclonal antibody (266A) raised against the human C1q receptor reacts with them.
Loss of human CR1- and murine Crry-like exons in human CR2 transcripts due to CR2 gene mutations.
Authors: Holguin M H , Kurtz C B , Parker C J , Weis J J , Weis J H 
Published: December 2022

Abstract
Analysis of the coding sequences of the murine Cr2 gene indicated that it contains two distinct regions of homology to the murine Crry, and human CR1 and CR2 genes. The last 15 short consensus repeats (SCR) of Cr2 are very similar to the 15 reported SCR of human CR2. These 15 SCR of Cr2, plus the transmembrane and cytoplasmic domains, make up a protein very similar in organization and sequence to the human CR2 gene product. Another Cr2 transcript contains the sequences encoding the previously described 15 SCR plus those encoding another six amino terminal SCR. These amino terminal SCR are very similar to those of Crry and the first six SCR seen within the CR1 long homologous repeats. Amino acid sequence similarity analysis, however, indicated that the sequences encoding the six amino terminal SCR of Cr2 evolved from a separate lineage of SCR than Crry and CR1, suggesting that the human counterparts to these additional Cr2 SCR had not been identified. Using the cDNA sequences specific for the amino terminal SCR of murine Cr2, the human counterparts were isolated and localized within the human CR2 gene between those nucleotides encoding the signal sequence and those encoding the first SCR of the mature human CR2 protein. Unlike the murine Cr2 gene products, these Crry/CR1-like sequences of the CR2 gene are not maintained in mature CR2 mRNA, and thus represent pseudoexons. DNA sequence analysis of the pseudoexon homologous to that encoding the first SCR of the murine Cr2 gene indicated that a stop codon has been introduced within the human coding sequence but that the 5' and 3' splice recognition sequences appear to be functional. Although the stop codon would block the translation of a transcript with this exon, it would not inhibit the incorporation of the exon within the mature CR2 transcript. Therefore, another mutation must have been introduced within the human CR2 gene such that both this exon and the other CR1/Crry-like exons are removed from mature CR2 transcripts.
Structural changes in the oligosaccharide chains of IgG in autoimmune MRL/Mp-lpr/lpr mice.
Authors: Mizuochi T , Hamako J , Nose M , Titani K 
Published: December 2022

Abstract
The structures of the asparagine-linked oligosaccharide chains of IgG from autoimmune arthritic MRL/Mp-lpr/lpr (MRL-lpr/lpr) mice and control MRL/Mp(-)+/+ (MRL(-)+/+) mice were investigated. Two subpopulations of IgG, M1-I and M1-II, were obtained from serum of MRL-lpr/lpr mice by column chromatography on protein A-Sepharose CL-4B. Although M1-I did not bind to the column, its elution was retarded, whereas M1-II was bound and was eluted in acidic buffer. IgG (Mn) from MRL(-)+/+ mice showed the same chromatographic behavior as M1-II. The structures of oligosaccharide chains liberated quantitatively by hydrazinolysis from IgG samples Mn, M1-I, M1-II, and a pooled mixture (M1) of M1-I and M1-II were determined by sequential exoglycosidase digestion, lectin (RCA120) affinity HPLC, and by methylation analysis. Their oligosaccharide structures were the same and shown to be biantennary complex-type chains +/- Gal beta 1----4GlcNAc beta 1----2Man alpha 1----6(+/- Gal beta 1----4GlcNAc beta 1----2Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(+/- Fuc alpha 1----6)GlcNAc. The proportion of each oligosaccharide in Mn and M1-II was the same but differed from that in M1-I where the degree of the galactosylation was significantly decreased which caused the change in the oligosaccharide pattern of total serum IgG (M1) of autoimmune MRL-lpr/lpr mice. This phenomenon, which is also found in total serum IgG of patients with rheumatoid arthritis, suggests that alteration of oligosaccharides in IgG may be a common feature in animals which develop arthritis with the production of rheumatoid factor regardless of species.
Cross-linking of Fc gamma receptors and surface antibodies. Theory and application.
Authors: Wofsy C , Goldstein B 
Published: December 2022

Abstract
B lymphocyte responses to the cross-linking of surface Ig (sIg) are known to be inhibited, when IgG is the cross-linking agent, by the concurrent binding of the Fc portion of the IgG to Fc gamma R. We present a mathematical framework for designing and analyzing experiments aimed at uncovering the inhibition mechanism(s). From our model, we calculate concentrations of receptors and ligands in the different cell surface states, at equilibrium or as a function of time. IgG can cross-link surface receptors in three ways, i.e., by bridging two sIg molecules without Fc binding, by bridging two sIg while binding as well to an Fc gamma R, and by binding to an Fc gamma R and only one sIg. We show how the concentrations or fractions of these distinct cross-linked states depend on experimentally manipulable variables, including the concentrations of intact IgG, bivalent and monovalent IgG fragments, and agents that block Fc binding. Then, using simple signal/response relationships, reflecting active and passive mechanisms of Fc-mediated inhibition, we simulate the results of a variety of experiments. In cases where published experimental results are available, we find that the qualitative predictions of our general model are consistent with the data and that comparisons of simulations with available data provide some quantitative information about the parameters governing the cell surface signaling events. In particular, comparison of model predictions with published experiments on the kinetics of IgG-induced inositol trisphosphate production indicate that sIg cross-links form more rapidly than sIg-Fc gamma R "co-cross-links." Further, IgG-sIg bonds stabilize Fc attachments, i.e., the dissociation of IgG from Fc gamma R is slowed significantly when the IgG is also cross-linked to sIg. Predictions of the model suggest other experiments and ways of presenting the data that will help to identify relationships between the molecular signaling events occurring on the cell surface and the various cellular responses.
IL-3 promotes basophilic differentiation of KU812 cells through high affinity binding sites.
Authors: Valent P , Besemer J , Kishi K , Kaltenbrunner R , Kuhn B , Maurer D , Lechner K , Bettelheim P 
Published: December 2022

Abstract
The myeloid precursor cell line KU812 exhibits a constitutive potential to differentiate into basophilic cells. In the present study, the influence of recombinant human (rh)IL-2, rhIL-3, and recombinant human granulocyte-macrophage-CSF on basophilic differentiation of KU812-F cells was studied. Of all cytokines tested, rhIL-3 induced a significant increase in formation of metachromatically granulated cells (from 10% in control cultures up to 30% in cultures supplemented with 100 U/ml of rhIL-3) as well as dose-dependent (1.5- to 3 fold) increase in cellular histamine in KU812-F cell cultures. In addition, KU812-F cells exposed to rhIL-3 bound more IgE antibody than cells cultured in control medium with up to 3.3-fold increases in the mean fluorescence intensity on days 2 and/or 5 compared with control (p less than 0.001). RhIL-3 failed to induce significant changes in expression of the Tac-reactive subunit of the IL-2R (CD25), surface aminopeptidase N (CD13), ICAM-1 Ag (CD54), or CD40 Ag on KU812-F cells. To investigate the mechanism of IL-3 action on KU812-F cells, receptor analyses were performed by using 125I-radiolabeled rhIL-3. Quantitative binding studies and Scatchard plot analyses revealed the presence of a single class of 1910 to 2460 high affinity IL-3-binding sites per KU812-F cell with an apparent dissociation constant of 1.22 to 2.35 x 10(-9) M. Together, these results show that rhIL-3 promotes basophilic differentiation of KU812-F cells through a specific receptor.
Signal transduction events in human basophils. A comparative study of the role of protein kinase C in basophils activated by anti-IgE antibody and formyl-methionyl-leucyl-phenylalanine.
Authors: Warner J A , MacGlashan D W 
Published: December 2022

Abstract
We have compared the transmembrane signals generated in human basophils by two distinct stimuli, anti-IgE antibody and FMLP (f-met peptide). Although both stimuli resulted in the activation of protein kinase C (PKC) and an increase in intracellular free calcium, there were substantial differences between the two which suggested that distinct signal transduction mechanisms were operating. We have confirmed an earlier observation that the cross-linking of IgE led to an increase in membrane PKC activity with no apparent concomitant loss of cytosolic PKC and established that in contrast, the univalent stimulus, f-met peptide, resulted in the canonical translocation of cytosolic PKC to the membrane. Furthermore, unlike anti-IgE-stimulated basophils, there was no clear relationship between the increase in PKC activity and the subsequent release of histamine. Two PKC inhibitors, staurosporine (0.1 to 1 nM) and sphingosine (25 to 50 microM), inhibited anti-IgE induced release, yet, potentiated the release of mediators after a challenge with 1 microM f-met peptide. Both stimuli led to an increase in the intracellular Ca2+ levels that correlated well with the release of histamine, however, the anti-IgE-induced responses were typically only 50% of those required to give equivalent histamine release when f-met peptide initiated release. Pharmacologic evidence suggested that the up-regulation of PKC was required for a full IgE-mediated Ca2+ response and that PKC contributed to the elevated Ca2+ levels that persist for up to 15 min after the addition of anti-IgE. In contrast, the PKC inhibitor, staurosporine, did not affect the initial increase in Ca2+ after the addition of f-met peptide but reduced the rate at which Ca2+ was removed from the cytosol. Experiments with the phorbol ester, PMA, suggested that substantial degranulation can occur in the absence of any increase in intracellular Ca2+. The addition of 10 ng/ml PMA 10 min before the addition of f-met peptide did not affect the magnitude of the initial Ca2+ transient but increased the rate at which Ca2+ levels returned to a stable baseline. Similar pretreatment with PMA almost completely abolished the anti-IgE antibody-induced Ca2+ response. These experiments, together with other previous data, suggest that the activation of PKC is a prodegranulatory component of the IgE-mediated signal transduction pathway, yet serves principally to modulate the Ca2+ signal when f-met peptide initiates release.
Tumor necrosis factor-alpha production of influenza A virus-infected macrophages and potentiating effect of lipopolysaccharides.
Authors: Nain M , Hinder F , Gong J H , Schmidt A , Bender A , Sprenger H , Gemsa D 
Published: December 2022

Abstract
Influenza A virus infections are commonly associated with symptoms that suggest involvement of TNF-alpha. In this study, we exposed human monocytes, rat alveolar macrophages, and murine PU5-1.8 macrophages to influenza A virus, strain Puerto Rico 8. We observed a productive infection that was accompanied by TNF-alpha mRNA accumulation, TNF-alpha release and subsequent cell death. TNF-alpha production was dependent on exposure to live virus, in contrast to IFN release that was also induced by UV-inactivated virus. Most strikingly, low amounts of LPS (1 to 10 ng/ml) from Escherichia coli or Haemophilus influenzae were capable of strongly potentiating TNF-alpha production from virus-infected macrophages. The potentiating effect of LPS was neither due to increased survival of macrophages nor to altered virus multiplication, enhanced TNF-alpha gene expression, discharge of intracellular TNF-alpha stores, or shifts in the kinetics of TNF-alpha release. Thus, low amounts of LPS, which could easily be present in vivo, may serve as a potent trigger signal for TNF-alpha production from macrophages that have been primed by influenza A virus infection. These data suggest that the frequently observed serious complications of combined influenza A virus and bacterial infections may be partially due to a high TNF-alpha production.