bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic AMP-independent effects of cholera toxin on B cell activation. II. Binding of ganglioside GM1 induces B cell activation.
Authors: Francis M L , Ryan J , Jobling M G , Holmes R K , Moss J , Mond J J 
Published: December 2022

Abstract
Although the physiologic function of gangliosides is unknown, evidence suggests they play a role in the regulation of cell growth. The binding of ganglioside GM1 by recombinant B subunit of cholera toxin (rCT-B) inhibited mitogen-stimulated B cell proliferation without elevating intracellular cAMP. CT-B paradoxically enhanced the expression of MHC class II (Ia) molecules and minor lymphocyte-stimulating determinants without altering the expression of some other immunologically relevant B cell surface Ag. Increased expression of Ia was not detected until 4 h after stimulation, kinetics similar to those seen when B cells are stimulated with anti-Ig antibody or IL-4, suggesting that the enhancement was not the result of redistribution of existing cell surface markers but rather the result of a new metabolic event. Both the inhibitory and stimulatory effects of CT-B could be blocked by incubation of CT-B with ganglioside GM1. Furthermore, enhancement of the CT-B-mediated effect was seen when additional ganglioside GM1 was incorporated into the B cell membrane. rCT-B with a mutation that interfered with its binding to ganglioside GM1 did not enhance Ia expression. Taken together, these results indicate that the observed effects of CT-B were most likely mediated through the binding of cell surface ganglioside GM1. CT-B-mediated stimulation of Ia expression provides a potential explanation for the previously described ability of CT-B to act as an immunoadjuvant. These results suggest that the binding of ganglioside GM1 has multiple B cell growth-regulating effects.
A pathogenic monoclonal antibody, G8, is characteristic of antierythrocyte autoantibodies from Coombs'-positive NZB mice.
Authors: Caulfield M J , Stanko D 
Published: December 2022

Abstract
With age, NZB mice develop anti-RBC autoantibodies resulting in the development of autoimmune hemolytic anemia. We now have evidence that this spontaneous autoantibody response consists of antibodies that are similar in specificity and Id expression to a pathogenic autoantibody (G8) that was cloned from an autoimmune NZB mouse. Similar to autoantibodies eluted from Coombs'-positive mouse E (MRBC), the G8 mAb recognizes native (unmodified) MRBC but not RBC from other species. Interestingly, G8 and four additional mAb bind with a higher titer to bromelain-treated MRBC than to native MRBC. Nucleotide sequence analysis reveals, however, that unlike "natural" antibodies that react solely with bromelain-MRBC, G8 is encoded by a J558 VH gene and a V kappa 12,13 L-chain gene. Thus G8 is clearly distinct from antibodies to bromelain-MRBC which are encoded by unrelated V genes. Instead, the sequence of the G8 VH chain was found to be nearly identical to that of an anti-DNA mAb derived from an MRL-lpr/lpr mouse. The results suggest Coombs'-positive autoantibodies from NZB mice are not derived from "natural" antibodies, but rather, consist of a restricted set of autoantibodies expressing the G8 IdX.
Association of the human Fc epsilon RI gamma subunit with novel cell surface polypeptides.
Authors: Schöneich J T , Wilkinson V L , Kado-Fong H , Presky D H , Kochan J P 
Published: December 2022

Abstract
It has recently been demonstrated that the gamma-subunits of the high affinity Fc epsilon RI are required for the cell surface expression of not only the Fc epsilon RI alpha-subunit, but also for the low affinity Fc gamma RIIIA alpha (CD16). In addition, formation of heterodimeric complexes of the gamma-subunit with the zeta- and eta-chains of the TCR have also been reported. The exact role of the gamma-subunit in the function of these receptors is not known. To gain additional insight into the association of the gamma-subunit with these and other cell surface polypeptides, we have generated a mAb, 4D8, directed against the human Fc epsilon RI gamma-subunit. Using this antibody we have been able to demonstrate that Fc epsilon RI alpha and Fc gamma RIIIA alpha are associated with Fc epsilon RI gamma at the cell surface. Furthermore, we have identified the expression of Fc epsilon RI gamma in HL60 and U937 cells, which are negative for the TCR, Fc epsilon RI, and Fc gamma RIII. Analysis of these cells reveals the presence of novel Fc epsilon RI gamma-associated polypeptides. These results suggest that Fc epsilon RI gamma plays a common functional role in a number of different receptor complexes. The availability of the anti-gamma antibody 4D8 will help to define this role, and allow the characterization of cell surface polypeptides that are associated with the Fc epsilon RI gamma-subunit.
Role of protein tyrosine phosphorylation in monokine induction by the staphylococcal superantigen toxic shock syndrome toxin-1.
Authors: Scholl P R , Trede N , Chatila T A , Geha R S 
Published: December 2022

Abstract
The staphylococcal superantigen toxic shock syndrome toxin-1 (TSST-1) is a potent inducer of IL-1 beta and TNF-alpha synthesis in human monocytes. As superantigens are high affinity ligands for MHC class II molecules, the induction of monokines by TSST-1 provides a biologically relevant model of MHC class II-mediated transmembrane signaling. In this study, we show that TSST-1 induces cytoplasmic protein tyrosine phosphorylation in the human monocytic cell line THP-1. This induction was greatly enhanced by cross-linking TSST-1 with biotin-avidin. The functional relevance of tyrosine phosphorylation induced by TSST-1 was demonstrated by the finding that three specific inhibitors of protein tyrosine kinases strongly inhibited the induction of IL-1 beta mRNA by TSST-1. These data suggest that protein tyrosine kinase activation plays a critical role in MHC class II-mediated transmembrane signalling by staphylococcal superantigens.
Formyl peptide stimulates and ATP gamma S potentiates [3H]cytidine 5'-diphosphate diglyceride accumulation in human neutrophils.
Authors: Stubbs E B , Walker B A , Owens C A , Ward P A , Agranoff B W 
Published: December 2022

Abstract
Although it is evident that the chemotactic peptide FMLP activates O2-formation in neutrophils via the phosphoinositidase-mediated second messenger system, it is less clear how endogenous priming agents such as ATP and platelet activating factor potentiate FMLP action. In our study, we have examined the possible effects of the stable ATP analog adenosine 5'-O-[3-thiotriphosphate] (ATP gamma S) on cellular levels of inositol 1,4,5-trisphosphate, [Ca2+]i and diglyceride (DG), in resting and in FMLP-stimulated neutrophils. Although all three measures were increased in the presence of FMLP, only the increase in DG was enhanced by pretreatment (priming) with ATP gamma S. We also measured the accumulation of the phosphoinositide cycle intermediate cytidine 5'-diphosphate (CDP)-DG to assess possible effects of priming on phosphoinositide resynthesis. The addition of FMLP to [3H]cytidine-prelabeled neutrophils elicited an increase in the accumulation of [3H]CDP-DG that was maximally enhanced in cells that were pretreated with cytochalasin B. The stimulated accumulation of [3H]CDP-DG was completely reversed by the addition of myo-inositol. Treatment of [3H]cytidine-prelabeled neutrophils with ATP gamma S (10-100 microM) resulted in a dose-dependent synergistic increase in FMLP-stimulated [3H]CDP-DG accumulation, whereas ATP gamma S alone had no effect. The observed increases in DG and in [3H]CDP-DG, in contrast to inositol 1,4,5-trisphosphate and [Ca2+]i responses, correlates well with the ATP gamma S-priming of FMLP-induced O2-formation. A similar potentiation of FMLP-induced stimulation of CDP-DG formation was also observed with platelet-activating factor. It is proposed that the priming of FMLP responses in neutrophils proceeds via a mechanism that selectively enhances DG production through a mechanism that is independent of FMLP-induced breakdown of phosphatidylinositol bisphosphate.
In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. II. Quantification of IL-4 mRNA, IFN-gamma mRNA, and IL-2 mRNA levels in the granulomatous livers, mesenteric lymph nodes, and spleens during the course of modulation.
Authors: Henderson G S , Lu X , McCurley T L , Colley D G 
Published: December 2022

Abstract
Parasite egg-induced granulomas are the primary pathogenic lesions in murine schistosomiasis mansoni. This cell-mediated granulomatous response is specific for soluble egg Ag and appears to be mediated predominantly by CD4+ Th2 cells. As infection progresses from the acute to the chronic phase, the cell-mediated anti-soluble egg Ag responses attenuate in a process termed modulation. In this study the hypothesis that modulation is effected by a chronic phase increase in Th2-inhibiting Th1 cell activity was investigated. Northern blot quantification of mRNA specific for the Th2 lymphokine, IL-4, and the Th1 lymphokines, IFN-gamma and IL-2, in the spleens, mesenteric lymph nodes, and granulomatous livers of mice infected for various lengths of time over the course of modulation was performed. Also, the capacity of mitogen- and Ag-stimulated spleen cells to produce message for these lymphokines was compared. Peak tissue levels of both IL-4 mRNA and IFN-gamma mRNA were seen in acutely infected mice, and levels of both messages declined as infection became chronic. Stimulated spleen cells from acutely infected mice also produced higher levels of IL-4 and IFN-gamma mRNA than cells from chronically infected mice. IL-2 mRNA was never detected in any tissue sample but was detected in the stimulated spleen cells, again with acute phase levels higher than chronic phase levels. Hence, this study shows no evidence for increased Th1 cell activity during chronic infection and suggests that modulation may be effected by a generalized suppression of lymphokine synthesis.
CD4+ Th2 response induced by Schistosoma mansoni eggs develops rapidly, through an early, transient, Th0-like stage.
Authors: Vella A T , Pearce E J 
Published: December 2022

Abstract
Data from recent studies of murine schistosomiasis mansoni have indicated that certain characteristics of this infection, such as eosinophilia and elevated IgE, are due largely to the induction of Th2-like immune responses by parasite ova. The present study was designed to examine more closely the genesis and development of these skewed Th responses to schistosome eggs. Accordingly, eggs isolated from infected mice were injected s.c. into normal mice. After inoculation, draining lymph node (LN) cells were recovered, phenotyped, and tested for their ability to proliferate and secrete IL-2 and IFN-gamma (as markers of Th1 function) and IL-4, IL-5, and IL-10 (Th2 cytokines). The results show a maximal LN enlargement of 40- to 100-fold by day 3 after egg inoculation. The CD4/CD8/B cell ratio at this time is similar to that in LN from normal mice, but increases in numbers of cells expressing very low levels of MEL-14 and high levels of Pgp-1 are evident by days 3 and 10, respectively. Surprisingly, the initial detectable Ag-specific response to schistosome eggs, observed at day 1, is the production of IFN-gamma. By day 3, LN cells are capable of proliferating and making IFN-gamma plus IL-2, IL-4, IL-5, and IL-10 when stimulated with soluble egg Ag and, therefore, appear Th0-like. After 7 to 10 days, IFN-gamma production is severely depressed but the response continues to be characterized by IL-4, IL-5, IL-10, and IL-2. Depletion studies indicate that CD4 cells are the major population responsible for Ag-mediated proliferation and cytokine production. Results show that schistosome eggs are autonomous inducers of vigorous Th2-like effector responses. Further, our data, from a system that utilizes an in vivo priming step, support the contentions that skewed Th responses develop via an intermediate Th0 stage is accompanied by a loss of the MEL-14 surface marker and an increase in Pgp-1 expression.
Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes.
Authors: Jiang Y , Beller D I , Frendl G , Graves D T 
Published: December 2022

Abstract
Monocytes play a critical role in defending the host against foreign organisms and in regulating the behavior of other cells. Monocytes circulate as nonadherent cells in the blood and migrate as adherent cells through tissues. Adhesion molecules mediate not only cell adhesion, but also migration, phagocytosis, and many other adhesion-dependent functions. Monocyte chemoattractant protein-1 (MCP-1) is thought to be responsible for monocyte recruitment in acute inflammatory conditions and may be an important mediator in chronic inflammation. In this study, immunofluorescence flow cytometry was used to determine whether MCP-1 can regulate the cell surface expression of adhesion molecules, particularly beta-2 and alpha-4 integrins and the leukocyte adhesion molecule-1. We found that MCP-1 induced expression of CD11c (p150,95 alpha-subunit) and CD11b (Mac-1 alpha-subunit), and caused little or no change of CD11a (lymphocyte function-associated Ag-1 alpha-subunit), very late activation Ag-4, or leukocyte adhesion molecule-1. We demonstrated that antibodies to beta-2 and alpha-4 integrins inhibited MCP-1-induced monocyte chemotaxis. We also showed that MCP-1 is capable of inducing IL-1 and IL-6, but not TNF production of monocytes. These results indicate that MCP-1 is not only a chemoattractant but also a novel cytokine with the capacity to regulate several parameters of monocyte function.
Preliminary identification and role of phosphodiesterase isozymes in human basophils.
Authors: Peachell P T , Undem B J , Schleimer R P , MacGlashan D W , Lichtenstein L M , Cieslinski L B , Torphy T J 
Published: December 2022

Abstract
We attempted to identify and establish the role of cyclic nucleotide phosphodiesterase (PDE) isozymes in human basophils by using standard biochemical techniques as well as describing the effects of isozyme-selective and nonselective inhibitors of PDE. The nonselective PDE inhibitors, theophylline and 3-isobutyl-1-methylxanthine, inhibited anti-IgE-induced release of histamine and leukotriene C4 (LTC4) from basophils. This inhibition was accompanied by elevations in cAMP levels. Rolipram, an inhibitor of the low Km cAMP-specific PDE (PDE IV), inhibited the release of both histamine and LTC4 from activated basophils and increased cAMP levels in these cells. In contrast, mediator release from basophils was not inhibited by either siguazodan or SK&F 95654, inhibitors of the cGMP-inhibited PDE (PDE III) or zaprinast, an inhibitor of the cGMP-specific PDE (PDE V). SK&F 95654 failed to elevate basophil cAMP in these experiments whereas zaprinast induced significant increases in cAMP content. The inhibitory effect of rolipram on mediator release was potentiated by siguazodan or SK&F 95654, but not by zaprinast. SK&F 95654 also enhanced the ability of rolipram to increase cAMP content. Forskolin, a direct activator of adenylate cyclase, inhibited IgE-dependent release of mediators from basophils and increased cAMP levels in these cells. These effects were enhanced by rolipram, but not by SK&F 95654 or zaprinast. The cell permeant analog of cAMP, dibutyryl cAMP, inhibited mediator release from these cells, a property not shared by either dibutyryl-cGMP or sodium nitroprusside, an activator of soluble guanylate cyclase. The presence of both PDE III and PDE IV was confirmed by partially purifying and characterizing PDE activity in broken cell preparations. Overall, these data lend support to the hypothesis that cAMP inhibits mediator release from basophils and suggest that the major PDE isozyme responsible for regulating cyclic AMP content in these cells is PDE IV, with a minor contribution from PDE III. However, the finding that zaprinast caused increases in cAMP without inhibiting mediator release indicates that cAMP accumulation is not invariably linked to an inhibition of basophil activation.
cis-acting regulatory elements abrogate allele-specific HLA class I gene expression in healthy individuals.
Authors: Lardy N M , Bakas R M , van der Horst A R , van Twuyver E , Bontrop R E , de Waal L P 
Published: December 2022

Abstract
Pedigree analysis of a Dutch family revealed the presence of an HLA-A "blanc" allele segregating with the HLA-B8, -Cw7, -DR3, -DR52, -DQ2 haplotype. Precipitation studies, using selected mAb and sera directed against conserved epitopes of HLA class I products, failed to detect the expression of a corresponding HLA-A locus product. cDNA nucleotide sequence analysis of the HLA-A "blanc" specificity showed that the obtained sequence was identical to the authentic HLA-A1 gene revealing no mutations, deletions or recombinations that could influence translation or transport of a putative translation product to the cell surface. Mitogen stimulation, EBV transformation, or treatment with rIFN-gamma and rTNF-alpha did not induce HLA-A1 expression. Furthermore, cell-mediated lympholysis analysis revealed that individuals carrying the nonexpressed HLA-A1 gene could mount a strong anti-HLA-A1 T cell response, indicating that HLA-A1 was not expressed during T cell ontogeny. Therefore, this study describes for the first time the allele-specific down-regulation of the expression of a classical HLA class I gene segregating in healthy individuals.
The antigen-processing mutant T2 suggests a role for MHC-linked genes in class II antigen presentation.
Authors: Riberdy J M , Cresswell P 
Published: December 2022

Abstract
.174xCEM.T2 (T2) is a human cell hybrid that has a large homozygous deletion within the MHC, including all of the functional class II genes. We have generated stable HLA-DR3 and H-2 I-Ak transfectants of T2 that express parental levels of class II molecules at the cell surface. T2.Ak transfectants fail to stimulate a hen egg lysozyme (HEL)-specific, I-Ak-restricted T cell when incubated with intact HEL. However, stimulation occurs if the appropriate HEL peptide is provided. The T2 cell line therefore has a defect in class II-restricted Ag processing. Biosynthetic studies demonstrate that the kinetics of I-Ak transport in T2.Ak are similar to the parental rates of transport, although the percentage of I-Ak molecules transported appears somewhat lower. I-Ak glycoproteins in T2.Ak associate normally with the I-chain, which appears to be proteolytically cleaved after transport through the Golgi apparatus in a similar fashion to that in the parent cell line, .174xCEM.T1 (T1). The DR alpha beta heterodimers in T2 differ from the parental phenotype in two ways. First, HLA-DR3 expressed in T2 does not have the epitope recognized by the DR3-specific mAb 16.23, although DR3 expressed in the parent does have the epitope. Second, the alpha beta subunits in the parent remain associated when exposed to SDS at room temperature, although those in T2 dissociate.
Identification and molecular cloning of tactile. A novel human T cell activation antigen that is a member of the Ig gene superfamily.
Authors: Wang P L , O'Farrell S , Clayberger C , Krensky A M 
Published: December 2022

Abstract
We have identified and cloned cDNA for a novel cell-surface protein that we have named Tactile for T cell activation, increased late expression. It is expressed on normal T cell lines and clones, and some transformed T cells, but no other cultured cell lines tested. It is expressed at low levels on peripheral T cells and is strongly up-regulated after activation, peaking 6 to 9 days after the activating stimulus. It is also up-regulated on NK cells activated in allogeneic cultures. It is not found on peripheral B cells but is expressed at very low levels on activated B cells. Tactile-specific mAb immunoprecipitates a band of 160 kDa when reduced and bands of 240, 180, and 160 kDa nonreduced. Using an antiserum produced with affinity-purified Tactile protein to screen a lambda gt11 library, we have identified Tactile cDNA. Northern blot analysis shows an expression pattern similar to that of the protein and transfection of COS cells with the full-length 5.2-kb cDNA results in cell-surface expression. Comparison with the sequence databanks show that Tactile is a member of the immunoglobulin gene superfamily, with similarity to Drosophila amalgam, the melanoma Ag MUC-18, members of the carcinoembryonic Ag family, the poliovirus receptor, and the neural cell adhesion molecule. The deduced primary sequence encodes a protein with three Ig domains, a long serine/threonine/proline-rich region typical of an extensively O-glycosylated domain, a transmembrane domain, and a 45 residue cytoplasmic domain. These data suggest that Tactile may be involved in adhesive interactions of activated T and NK cells during the late phase of the immune response.
Regulation of locomotion and cell-cell contact area by the LFA-1 and ICAM-1 adhesion receptors.
Authors: Dustin M L , Carpen O , Springer T A 
Published: December 2022

Abstract
We demonstrate complementary differences in the behavior of B lymphoblastoid cells adhering to LFA-1 or its counter-receptor ICAM-1. The interaction of B lymphoblastoid cells with glass-supported planar bilayers bearing LFA-1 or ICAM-1 was observed by time-lapse video microscopy, and the distribution of adhesion receptors on cells interacting with the planar bilayers was studied by immunofluorescence microscopy. B lymphoblasts formed a large contact area and crawled rapidly (up to 25 microns/min) on planar bilayers bearing ICAM-1. In contrast, these cells attached to planar bilayers bearing LFA-1 through a fixed point about which the cells actively pivoted, using a single stalk-like projection. Phorbol ester-stimulated lymphoblasts, which adhere more strongly to ICAM-1-bearing substrates than unstimulated lymphoblasts, were still capable of locomotion on ICAM-1. Phorbol ester stimulation of B lymphoblasts on planar bilayers bearing LFA-1 promoted a rapid conversion from "stalk" attachment to symmetrical spreading of the cell on the substrate. Cellular LFA-1 remained uniformly distributed on the cell surface during interaction with bilayers bearing purified ICAM-1 as determined by immunofluorescence. In contrast, ICAM-1 was concentrated in the stalk-like structure through which the unstimulated B lymphoblasts adhered to LFA-1 in planar bilayers, but ICAM-1 immunofluorescence became more uniformly distributed over the cell surface within minutes of phorbol ester addition. Neither LFA-1 or ICAM-1 colocalized with the prominent staining of filamentous actin in the ruffling membrane regions. Interaction through cell surface LFA-1 and ICAM-1, 2, or 3 promotes different cellular morphologies and behaviors, the correlation of which with previously observed patterns of lymphocyte interaction with different cell types is discussed.