bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional antagonism between vitamin D3 and retinoic acid in the regulation of CD14 and CD23 expression during monocytic differentiation of U-937 cells.
Authors: Oberg F , Botling J , Nilsson K 
Published: December 2022

Abstract
1,25 alpha-Dihydroxicholecalciferol (VitD3) and retinoic acid (RA) are important regulators of the proliferation and differentiation of several cell types. This paper describes how the expression of the monocyte-macrophage Ag, CD14, and the low affinity Fc receptor for IgE, CD23, were inversely regulated during VitD3- and RA-induced monocytic differentiation of human U-937 monoblasts. PMA induced the expression of both CD14 and CD23 mRNA and protein. Exposure to VitD3 rapidly induced the de novo expression of CD14 mRNA and protein. The addition of cycloheximide completely blocked the VitD3 induction of CD14 mRNA expression, indicating that the induction was dependent on ongoing protein synthesis. While inducing CD14 expression, VitD3 concomitantly suppressed the basal, PMA-, and RA-inducible CD23 expression in a dose-dependent manner. In contrast, U-937 cells induced by RA strongly increased their expression of CD23 mRNA and protein, whereas they completely lacked detectable CD14 cell surface or mRNA expression. Furthermore, the VitD3- and the PMA-induced CD14 expression was inhibited as a temporal consequence of the RA-induced differentiation. The results suggest that there exists a functional antagonism between VitD3 and RA that may have important implications for the regulation of certain immune and inflammatory responses through their inverse effects on CD14 and CD23 gene expression.
Enhancement of antigen-induced bronchoconstriction after intravascular complement activation with cobra venom factor. Reversal by granulocyte depletion.
Authors: Regal J F , Fraser D G , Anderson D E , Solem L E 
Published: December 2022

Abstract
Our previous studies have demonstrated that activation of the C system with cobra venom factor (CVF) in a passively sensitized guinea pig results in an enhanced bronchoconstrictor response to Ag but not to other constrictor agents. Thus, our immediate goal was to determine the mechanism of the CVF-induced enhancement of the Ag-induced bronchoconstriction. Isolated airways from sensitized guinea pigs that had been treated with CVF responded normally to Ag. Because such a system lacks the normal circulating cell populations, we hypothesized that the CVF-induced enhancement of the Ag-induced bronchoconstriction was dependent on the presence of circulating white blood cells or platelets. Guinea pigs were depleted of circulating granulocytes, platelets, or both using specific antisera and the effect on the CVF-induced enhancement of the Ag-induced bronchoconstriction was determined. We found that CVF treatment did not result in an enhanced Ag-induced bronchoconstriction in guinea pigs depleted of either granulocytes or both granulocytes and platelets. However, the enhanced response was still apparent in guinea pigs depleted of just platelets. We investigated the effects of CVF itself and found that CVF treatment did not alter the number, or percentages, of different cell populations in the bronchoalveolar lavage, did not alter the protein or albumin content of the lavage fluid or the wet:dry ratio of the lung. In addition, CVF did not cause an increase in airway microvascular permeability as assessed by leakage of Evans blue. However, CVF did substantially increase granulocytes sequestered in the lung as measured by increased myeloperoxidase content. Thus, C activation by CVF results in an increase in neutrophils in the lung and an enhanced Ag-induced bronchoconstriction dependent on the presence of circulating granulocytes. These studies suggest that C activation and/or retention of granulocytes in the lung may be important in determining the severity of an Ag-induced bronchoconstriction.
Effect of docosahexaenoic acid on the generation of platelet-activating factor by eosinophilic leukemia cells, Eol-1.
Authors: Shikano M , Masuzawa Y , Yazawa K 
Published: December 2022

Abstract
Human eosinophilic leukemia (Eol-1) cells were examined for their ability to generate platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) (PAF) and the effect of supplementation of docosa-hexaenoic acid (C22:6n-3) (DHA) on the PAF synthesis was explored in relation to the fatty acid composition of phospholipids and the liberation of arachidonic acid (C20:4n-6 AA). Although undifferentiated cells did not produce PAF, the exposure of IFN-gamma differentiated Eol-1 to generate PAF in response to the Ca-ionophore. In addition, the IFN-gamma-treated cells acquired the ability to release free fatty acids, approximately 55% of which was found to be AA. When DHA was supplemented into the culture of Eol-1 for 24 h, PAF production decreased by 40 to 50% at concentrations of 3 to 10 microM. On the other hand, supplementation of 10 microM eicosapentaenoic acid (C20:5n-3) did not significantly decrease PAF production. With the supplementation of 10 microM DHA, DHA levels in phospholipid subclasses, including alkylacylglycerophosphocholine, were greatly increased with concurrent decreases in other unsaturated fatty acids. In these cells, the liberation of AA in response to an ionophore was decreased by 55%. Even when DHA was enriched in phospholipids, DHA release in response to ionophore stimulation was almost negligible, indicating that the DHA moiety of phospholipids is not susceptible to the action of phospholipase A2. Furthermore, DHA supplementation appeared to attenuate phospholipase A2 reaction by some unknown mechanism because the decrease in AA release was much more than that for the AA level in phospholipids. Acetyl-CoA:1-alkylGPC acetyltransferase activity of stimulated cell lysate was also reduced by DHA supplementation but the reduction was much less when compared with that of PAF synthesis or AA release. These results implicated that enrichment of DHA attenuates enzymic reactions for PAF synthesis, mainly the initial reaction catalyzed by AA-specific phospholipase, and thereby reduces PAF synthesis in Eol-1.
Effects of exogenous eicosapentaenoic acid on generation of leukotriene C4 and leukotriene C5 by calcium ionophore-activated human eosinophils in vitro.
Authors: Thien F C , Hallsworth M P , Soh C , Lee T H 
Published: December 2022

Abstract
Exogenous eicosapentaenoic acid (EPA) has been compared with exogenous arachidonic acid (AA) for its ability to modulate the oxidative metabolism of membrane-derived arachidonic acid by the 5-lipoxygenase pathway in ionophore-activated human eosinophils, and for its suitability as a parallel substrate in this pathway. Products were quantitated by specific RIA and tetraene and pentaene leukotrienes (LT) were separated by reverse-phase HPLC. Eosinophils were preincubated with control buffer, exogenous EPA or AA and stimulated optimally with 10 microM calcium ionophore (A23187) for 15 min. Mean generation of LTC4 in the absence of fatty acid was 6.0 = 1.1 ng/10(6) eosinophils (mean = SEM, n = 5). In the presence of EPA, the amount of LTC4 generated rose to peak at 16.5 +/- 1.9 ng/10(6) eosinophils at 10 micrograms/ml EPA and then fell to 8.3 +/- 3.1 ng/10(6) cells at 40 micrograms/ml EPA. The EPA derivative, LTC5 was first detectable at 5 micrograms/ml EPA with 4.8 +/- 1.2 ng/10(6) cells and gradually rose with increasing dose of EPA to be maximal at 40 micrograms/ml with 12.7 +/- 2.2 ng/10(6) cells. Identity of the LTC5 was confirmed by an identical retention time to synthetic LTC5 standard, immunoreactivity to a specific antibody against LTC4 and LTC5 and a typical UV absorbance spectrum. When eosinophils were preincubated with AA and similarly stimulated, LTC4 generation gradually increased from a baseline of 6.7 +/- 0.7 ng/10(6) cells in the absence of fatty acid to reach a maximum of 12.9 +/- 0.8 ng/10(6) cells at 40 micrograms/ml of AA. Total LTC generation was nearly twofold more with cells incubated with EPA than with cells incubated with AA (p &lt; 0.05). Thus, EPA does not suppress LTC generation from eosinophils but stimulates it at lower doses and is a substrate for LTC5 generation.
Engraftment and activity of anti-CD3-activated human peripheral blood lymphocytes transferred into mice with severe combined immune deficiency.
Authors: Murphy W J , Conlon K C , Sayers T J , Wiltrout R H , Back T C , Ortaldo J R , Longo D L 
Published: December 2022

Abstract
Human PBL (huPBL) were activated with anti-CD3 mAb in vitro and then were transferred into mice with severe combined immune deficiency (SCID) to determine the effect of activation on engraftment and to determine if the engrafted human cells could provide antitumor effects in mice. Some mice were also treated with human rIL-2 after huPBL transfer. Mice were analyzed 6 to 8 wk after cell transfer and the number of human cells in the peripheral lymphoid organs was determined. Mice receiving anti-CD3-activated huPBL demonstrated a significant increase in the incidence of human T cell engraftment in the periphery as assessed by flow cytometry. Human cells were also detected in the murine thymus after anti-CD3 stimulation indicating that human T cells can migrate to the murine thymus provided that they are activated before the transfer. The transfer of anti-CD3-activated huPBL also resulted in an xenogeneic graft-vs-host reaction manifested primarily by proliferation of murine splenic hemopoietic cells. When SCID mice received the human colon carcinoma HT29, the concurrent transfer of anti-CD3-activated human cells resulted in a significant increase in survival. However, the human cells displayed low cytolytic activity toward human tumor targets when they were recovered from the lymphoid organs of the SCID recipients. Supernatants from the anti-CD3-activated cells were able to inhibit the growth of HT29 in vitro, partly because of the presence of IFN-gamma, suggesting that the human T cells are producing cytokines in vivo that have antitumor effects. Thus, the use of anti-CD3-activated huPBL in SCID mice may be of value for optimizing human cell engraftment in the human/mouse lymphoid chimeras and may be used to evaluate potential anti-neoplastic therapies that employ human effector cells.
Human B cell proliferation and Ig secretion induced by recombinant CD40 ligand are modulated by soluble cytokines.
Authors: Armitage R J , Macduff B M , Spriggs M K , Fanslow W C 
Published: December 2022

Abstract
Recombinant human CD40 ligand (hCD40L) was expressed on the surface of CV1/EBNA cells and examined for its ability to induce proliferation and Ig secretion from human B cells in the presence or absence of soluble cytokines. hCD40L was directly mitogenic in a dose-dependent fashion for purified tonsil B cells with maximal proliferation occurring at days 5 to 7. Proliferation induced by CD40L was significantly enhanced in the presence of IL-2, IL-4, or IL-10 and strongly suppressed by transforming growth factor-beta. Although IL-5, TNF-alpha, and IFN-gamma had no stimulatory effect in the presence of hCD40L alone, if IL-4 was also present in cultures, these cytokines enhanced the proliferative response above that seen with IL-4 alone. Interestingly, in the absence of IL-4, IFN gamma had an inhibitory effect on hCD40L-induced proliferation. Although CD40L alone did not enhance Ig secretion, addition of IL-2 or IL-10 to the cultures significantly elevated the levels of IgM, IgG1, and IgA that were observed. Addition of IL-4 to the cultures did not enhance secretion of these isotypes but had a weak inhibitory effect. However, CD40L-mediated induction of IgG4 and IgE was dependent on the presence of IL-4. Of the cytokines examined, only IL-10 enhanced IgE secretion under these conditions. Although transforming growth factor-beta only partially inhibited secretion of IgM, IgG1, and IgA, it was strongly suppressive for IgG4 and IgE production. Our data demonstrate that proliferation and Ig secretion induced in the presence of CD40L can be modulated in a positive and negative fashion by soluble cytokines. IL-2 and IL-10 specifically enhance IgM, IgG1, and IgA production although IL-4, despite costimulating B cell proliferation, does not augment secretion of these isotypes but provided an essential cosignal with CD40L for the production of IgG4 and IgE.
Photoaffinity labeling of the T cell receptor on living cytotoxic T lymphocytes.
Authors: Romero P , Maryanski J L , Luescher I F 
Published: December 2022

Abstract
Using a direct binding assay based on photoaffinity labeling, we have studied the interaction of an antigenic peptide with MHC class I molecules and the TCR on living cells. Two photoreactive derivatives of the H-2Kd (Kd) restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) were used. The first derivative contained an N-terminal photoreactive iodo, 4-azido salicyloyl (IASA) group and biotin on the TCR contact residue Lys259 [IASA-YIPSAEK(biotin)I]. As previously described, this derivative selectively bound to and labeled the Kd molecule. The second photoreactive compound, the isomeric biotin-YIPSAEK(IASA)I, also efficiently bound to the Kd molecule, but failed to label this protein. A CTL clone derived from a mouse immunized with this derivative recognized this conjugate but not the parental P. berghei circumsporozoite peptide or the [IASA-YIPSAEK-(biotin)I] derivative in an Kd-restricted manner. Incubation of the cloned CTL cells with biotin-YIPSAEK(IASA)I, but not its isomer, followed by UV irradiation resulted in photoaffinity labeling of the TCR-alpha chain that was dependent on the conjugate binding to the Kd molecule. The TCR labeling was partially inhibited by anti-LFA 1 and anti-ICAM1 mAb, but was increased by addition of beta 2m or soluble KdQ10. The exquisite labeling selectivity of the two photoprobes opens a new, direct approach to the molecular analysis of antigen presentation and recognition by living CTL.
lpr T cells are necessary for autoantibody production in lpr mice.
Authors: Sobel E S , Cohen P L , Eisenberg R A 
Published: December 2022

Abstract
Mice homozygous for the gene Ipr develop a spectrum of autoantibodies closely resembling that of human SLE. Previous work has shown that the lpr defect must be expressed in the T cells that hyperproliferate and in the B cells that produce autoantibodies. Although autoantibody production in lpr mice requires T cells, it is not known whether these need to be lpr T cells. To ask whether normal (+/+) T cells can help lpr B cells produce autoantibodies, we have constructed chimeras containing mixtures of lpr-derived and normal-derived lymphoid cells, and have selectively eliminated the lpr-derived T cells by in vivo treatment with monoclonal anti-Thy-1 of the appropriate allotype. A mixture of T cell-depleted bone marrow from congenic strains of normal and lpr mice differentially marked by Ig H chain allotype and Thy-1 alleles was transferred into lethally irradiated lpr mice. The mice received weekly injections of either anti-Thy-1.2 to deplete specifically lpr T cells or an isotype-matched irrelevant control mAb. Absence of lpr-derived T cells in the experimental group was documented by immunofluorescence. In mice treated with control antibody, autoantibodies of Ipr origin were present in high titers, as determined by allotype-specific ELISA. In contrast, mice depleted of lpr-derived T cells had greatly reduced titers of antichromatin and rheumatoid factor. These mice also had increased levels of serum total IgM and IgG2a of +/+ origin. Parallel experiments were performed using a combination of two lpr marrow sources, also differentially marked by Ig H chain allotype and Thy-1 expression. Mice depleted of Thy-1.2-bearing T cells produced autoantibodies of both allotypes due to the presence of Thy-1.1-bearing T cells of Ipr origin. These data indicate that autoantibody production in lpr mice requires expression of the lpr gene in those T cells that provide help.
Increased IL-6 production and IL-6-mediated Ig secretion in murine host-vs-graft disease.
Authors: Vandenabeele P , Abramowicz D , Berus D , Van der Heyden J , Grooten J , Donckier V , Hooghe-Peters E L , Goldman M , Fiers W 
Published: December 2022

Abstract
BALB/c mice neonatally injected with semiallogenic (A/J x BALB/c)F1 splenocytes develop a host-vs-graft (HVG) reaction between host T cells and donor B cells, resulting in hypergammaglobulinemia, splenomegaly, and increased serum levels of various autoantibodies. This syndrome is associated with a polyclonal activation of the donor-derived B cells. High serum levels of IL-6 were found in 4-wk-old mice undergoing HVG disease (mean +/- SEM, 132 +/- 93 as compared with 12 +/- 2 in control mice, p &lt; 0.05). Also supernatants of spleen cell cultures from HVG mice contained increased levels of IL-6. In situ hybridization and cell depletion experiments demonstrated that host macrophages were responsible for this pathologic IL-6 secretion. The spontaneous in vitro production of autoreactive antibodies by donor B cells from HVG mice was further enhanced by adding human rIL-6, whereas addition of human rIL-1 beta, human rIL-2, murine rIL-4, murine rIL-5, or combinations of these cytokines had no effect. Finally, addition of blocking anti-IL-6 and anti-IL-6 receptor mAb markedly reduced hyper IgG1 production in cultures of spleen cells from HVG mice. These data suggest that an increased production of IL-6 by persistently stimulated host macrophages is involved in the activation of donor B cells leading to HVG disease.
Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure.
Authors: Zhang Y , Lee T C , Guillemin B , Yu M C , Rom W N 
Published: December 2022

Abstract
Idiopathic pulmonary fibrosis (IPF) and asbestosis are fibrotic interstitial lung diseases characterized by alveolar wall fibrosis with accumulation of extracellular matrix, interstitial remodeling, and increased numbers of activated alveolar macrophages. Animal models and in vitro studies have shown that macrophage cytokines, namely IL-1 beta and TNF-alpha, play significant roles in the development of fibrosis. We found significant increases for TNF-alpha release in both diseases (p &lt; 0.01) and a significant increase for IL-1 beta release in asbestosis compared to normal controls (p &lt; 0.01). Also, the mRNA expression of these cytokines was increased in alveolar macrophages from patients with IPF or asbestosis compared with normals. The level of TNF-alpha release in macrophage supernatants correlated with the number of neutrophils per milliliter bronchoalveolar lavage fluid returned. Chrysotile, crocidolite, amosite asbestos, and silica stimulated IL-1 beta and TNF-alpha release and up-regulated their respective mRNA in macrophages or monocytes. To evaluate the role of IL-1 beta and TNF-alpha in the accumulation of extracellular matrix, we studied collagen types I and III and fibronectin gene expression in human diploid lung fibroblasts after short term (2 h) serum-free exposure to recombinant cytokines. Both cytokines up-regulated these genes 1.5- to 3.6-fold. These cytokines have the potential to influence the remodeling and fibrosis observed in the lower respiratory tract in IPF and asbestosis.
Surface transport and internalization of the membrane IgM H chain in the absence of the Mb-1 and B29 proteins.
Authors: Cherayil B J , MacDonald K , Waneck G L , Pillai S 
Published: December 2022

Abstract
The micron IgH chain is one component of the membrane IgM complex, the endocytic and signal transducing receptor for Ag on the surface of B lymphocytes. It is transported to the cell surface in association with three other B cell-specific proteins, an L chain and the products of the mb-1 and B29 genes. The roles played by these various proteins in mediating the functions of the complex are unclear. To analyze micron function in the absence of other lymphoid-specific proteins, we first attempted to express micron on the surface of nonlymphoid cells. Deletion of the CH1 domain was sufficient to allow surface expression of this protein in transfected COS cells as well as in mouse L cells. To determine whether this extracellularly truncated micron was capable of endocytosis, we used an assay to detect the internalization of anti-mu antibody bound to the surface of transfected cells expressing the protein. Under both cross-linking and non cross-linking conditions, the CH1-deleted micron protein was internalized in endocytic vesicles. We conclude from these observations that a) the CH1 domain of micron contains a retention signal, the elimination of which allows surface transport of this protein, and b) micron by itself is capable of at least one of the functions of the membrane IgM complex.
Organization of the murine Cd22 locus. Mapping to chromosome 7 and characterization of two alleles.
Authors: Law C L , Torres R M , Sundberg H A , Parkhouse R M , Brannan C I , Copeland N G , Jenkins N A , Clark E A 
Published: December 2022

Abstract
Murine CD22 (mCD22) is a B cell-associated adhesion protein with seven extracellular Ig-like domains that has 62% amino acid identity to its human homologue. Southern analysis on genomic DNA isolated from tissues and cell lines from several mouse strains using mCD22 cDNA demonstrated that the Cd22 locus encoding mCD22 is a single copy gene of &lt; or = 30 kb. Digestion of genomic DNA preparations with four restriction endonucleases revealed the presence of restriction fragment length polymorphisms (RFLP) in BALB/c, C57BL/6, and C3H strains vs DBA/2J, NZB, and NZC strains, suggesting the presence of two or more Cd22 alleles. Using a mCD22 cDNA clone derived from the BALB/c strain, we isolated genomic clones from a DBA/2J genomic library that contained all the exons necessary to encode the full length mCD22 cDNA. Fifteen exons, including exon 3 that encodes the translation start codon, were identified. Each extracellular Ig-like domain of mCD22 is encoded by a single exon. A comparison between the nucleotide sequences of the BALB/c CD22 cDNA and the exons of the DBA/2J CD22 genomic clones revealed an 18-nucleotide deletion in exon 4 (encoding the most distal Ig-like domain 1 of mCD22) of the DBA/2J genomic sequence in addition to a number of substitutions, insertions, and deletions in other exons. These nucleotide differences were also present in a cDNA clone isolated from total RNA of LPS-activated DBA/2J splenocytes by reverse transcription-polymerase chain reaction. The Cd22 locus was mapped to the proximal region of chromosome 7, a region sytenic to human chromosome 19q, close to the previously reported loci, Lyb-8 and Mag (a homologue of Cd22). An antibody (CY34) against the Lyb-8.2 B cell marker reacted with a BHK transfectant expressing the full length mCD22 cDNA, thus demonstrating that Lyb-8 and Cd22 loci are identical. Furthermore, a rat anti-mCD22 mAb, NIM-R6, bound to sIgM+ DBA/2J B cells, confirming the expression of a CD22 protein by the Cd22a/Lyb-8a allele.