bluuebunny/crossref_metadata_2025_split huggingface dataset:
RANTES, a monocyte and T lymphocyte chemotactic cytokine releases histamine from human basophils.
Authors: Kuna P , Reddigari S R , Schall T J , Rucinski D , Viksman M Y , Kaplan A P 
Published: January 2023

Abstract
Chemotaxis of different populations of cells and release of proinflammatory mediators in response to antigenic stimulation are important processes in allergic diseases. These lead to the late phase response, a hallmark of chronic allergic diseases. Recombinant RANTES, a member of the "intercrine/chemokine" family of cytokines, has been previously shown to be chemotactic for monocytes and T cells of memory/helper phenotype. In this manuscript, we show that it is capable of inducing histamine release from human basophils at concentrations as low as 10(-10) M and compare its activity with that of monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), another intercrine/chemokine. RANTES (10(-7) M) caused histamine release from the leukocytes of 26 of 33 donors tested (mean 21.8 +/- 3.1%). In the same group of donors, MCAF/MCP-1, goat anti-human IgE (anti-IgE; 1 microgram/ml), and FMLP (10(-5) M) released 41.1 +/- 2.9%, 40.5 +/- 4.6%, and 44 +/- 3.1% histamine, respectively. The percent histamine release by RANTES in atopic vs nonatopics was 30.3 +/- 6.7 and 16.5 +/- 2.4, respectively (p less than 0.05), and histamine release by RANTES correlated significantly with histamine release by MCAF (r = 0.69; p less than 0.001) but not with histamine release by anti-IgE (r = 0.29; p greater than 0.05). Histamine release by RANTES and MCAF/MCP-1 was extremely rapid, reaching a maximum within 1 min. RANTES was also shown to activate highly purified basophils (80% pure), and its activity was inhibited by a polyclonal anti-RANTES antibody. At a suboptimal concentration (6 x 10(-9) M), RANTES did not prime basophils to enhance histamine release by secretagogues such as anti-IgE, C5a, or FMLP. On the other hand, preincubation of basophils with RANTES or MCAF/MCP-1 desensitized basophils to either factor but not to anti-IgE, C5a, or FMLP. Preincubation of basophils with pertussis toxin markedly diminished the basophil response to either RANTES or MCAF/MCP-1. These results suggest that RANTES and MCAF/MCP-1: 1) are potent activators of basophils; 2) may function via the same, or a closely related, receptor system in basophils; and 3) may represent a link between activation of monocytes, lymphocytes, and basophils in inflammatory disorders such as the late phase allergic reaction.
CD34+ bone marrow cells are infected with HIV in a subset of seropositive individuals.
Authors: Stanley S K , Kessler S W , Justement J S , Schnittman S M , Greenhouse J J , Brown C C , Musongela L , Musey K , Kapita B , Fauci A S 
Published: January 2023

Abstract
Individuals infected with HIV frequently develop cytopenias and suppressed hematopoiesis. The role of direct HIV infection of hematopoietic progenitor cells in this process has not been defined. In this study, purified CD34+ bone marrow progenitor cells from 74 Zairian and American patients were studied by both coculture viral isolation and polymerase chain reaction for evidence of HIV infection. A total of 36.5% of Zairian and 14% of American patients had HIV infection of the CD34+ cell subset, with as many as 1 in 500 CD34+ cells infected. Most of the Zairian patients in this study had advanced HIV infection and markedly decreased CD4/CD8 T lymphocyte ratios (mean 0.160 +/- 0.08), and no laboratory value predicted the presence of infection in the CD34+ subset of a given Zairian individual. In contrast, American patients with CD34+ cell infection had total CD4 cells less than 20/mm3 and a greater decrease of the CD4/CD8 T lymphocyte ratio compared to seropositive Americans without CD34+ cell infection (p = 0.003). Hematopoiesis, studied by methylcellulose colony assays, was depressed in all seropositive patients studied with no significant further suppression when CD34+ cells were infected. Thus, CD34+ bone marrow progenitor cells are infected in vivo in a subset of seropositive individuals and may serve as an additional reservoir of virus in HIV-infected individuals.
Production of monocyte chemoattractant protein-1 by inflamed synovial tissue and cultured synoviocytes.
Authors: Villiger P M , Terkeltaub R , Lotz M 
Published: January 2023

Abstract
This study analyzes the expression of monocyte chemoattractant protein-1 (MCP-1) by inflamed synovial tissue and defines its regulation in cultured synoviocytes. Synoviocytes from patients with rheumatoid arthritis and osteoarthritis express the 0.7-kb MCP-1 mRNA. Stimulation of synoviocytes with IL-1, TNF-alpha, LPS, platelet-derived growth factor, and transforming growth factor-beta-1, but not with basic fibroblast growth factor causes a marked increase in MCP-1 mRNA levels. Expression of the MCP-1 gene is inducible by activators of the protein kinase A (cAMP) and C (PMA) signal transduction pathways and is differentially regulated by the steroids dexamethasone and retinoic acid. Cultured synoviocytes de novo synthesize 12-, 15-, and 15.2-kDa MCP-1 proteins, which increase after stimulation with IL-1. Synovial tissues from donors without joint disease and from patients with rheumatoid or osteoarthritis were analyzed for MCP-1 mRNA expression by in situ hybridization. In these samples MCP-1 mRNA expressing cells were predominantly found in the sublining cell layers, whereas specimens of normal synovial tissue contained only few positive cells. These results identify synoviocytes as a source of MCP-1. Its expression is controlled by peptide regulatory factors that are known to be present in arthritic joints. Detection of cells producing MCP-1 mRNA in synovial tissues from patients with arthritis shows that this gene is expressed in vivo and suggests that MCP-1 can play a role in recruiting monocytes in joint inflammation.
Role of Ly-6A/E and T cell receptor-zeta for IL-2 production. Phosphatidylinositol-anchored Ly-6A/E antagonizes T cell receptor-mediated IL-2 production by a zeta-independent pathway.
Authors: Codias E K , Fleming T J , Zacharchuk C M , Ashwell J D , Malek T R 
Published: January 2023

Abstract
Ly-6A/E molecules were originally implicated in regulation of T cell activation because anti-Ly-6A/E mAb induce IL-2 production. More recently we have shown that anti-Ly-6A/E also inhibits IL-2 production induced by anti-CD3. In the present study we used mutant and transfected cell lines that varied in expression of Ly-6A/E or TCR-zeta to test whether the positive and negative modulations of IL-2 production by anti-Ly-6A/E occur by distinct mechanisms. Anti-Ly-6A/E inhibited anti-CD3-induced IL-2 production for Ly-6E.1-transfected EL4J cells, but did not affect IL-2 production of the parental Ly-6A/E-negative EL4J cells. These results indicate that TCR-mediated IL-2 production can occur in the absence of Ly-6A/E expression and establish that anti-Ly-6A/E-induced inhibition of IL-2 production was the result of antibody binding to Ly-6A/E. As expected, MA5.8 (zeta-negative) or CT108 (zeta-truncated) variants of the 2B4.11 T cell hybridoma did not produce IL-2 when stimulated with anti-Thy-1 or anti-Ly-6A/E mAb. In contrast, anti-Ly-6A/E inhibited anti-CD3-induced IL-2 production by MA5.8 and CT108. Furthermore, anti-Ly-6A/E-induced IL-2 production was restored for zeta-transfected MA5.8. Thus, although induction of IL-2 by anti-Ly-6A/E depends on zeta expression, inhibition of IL-2 by anti-Ly-6A/E occurs by a zeta-independent mechanism. Interestingly, anti-Ly-6A/E, but not anti-Thy-1, inhibited anti-CD3-induced IL-2 production by MA5.8 and Ly-6E.1-transfected EL4J. Therefore, inhibition of IL-2 production by anti-Ly-6A/E was not a general property of a mAb binding to a phosphatidylinositol-linked molecule, as has been suggested for induction of IL-2 production. Taken together these data suggest that the molecular mechanisms of induction and inhibition of IL-2 production by anti-Ly-6A/E are separable and expression of TCR-zeta is one variable that distinguishes these two pathways.
A conditional secretory mutant in an Ig L chain is caused by replacement of tyrosine/phenylalanine 87 with histidine.
Authors: Dul J L , Burrone O R , Argon Y 
Published: January 2023

Abstract
The kappa-chain of the myeloma MOPC 21 is an unusual L chain, in that it is not secreted unless complexed with a H chain. This nonsecreted kappa-chain seems to be retained in the endoplasmic reticulum in association with the protein BiP/GRP78, both in myeloma cells and when expressed in COS-1 fibroblasts. By assaying the fate of the MOPC 21 kappa-chain and its mutated derivatives in COS-1 cells, we show that the cause of the nonsecreted phenotype is the presence of histidine in position 87 of the variable domain. When this amino acid is changed back to the tyrosine that usually occupies position 87, secretion of the unassembled kappa-chain is restored. As in B lymphoid cells, co-expression of gamma H chains in COS-1 cells complements the mutation in the L chain, and rescues secretion of the arrested kappa. Thus, the presence of histidine at position 87 creates a conditional L chain secretory mutant: it is not compatible with normal transport of free L chain, but can be rescued in the presence of H chain.
Examination of four HLA class I pseudogenes. Common events in the evolution of HLA genes and pseudogenes.
Authors: Geraghty D E , Koller B H , Pei J , Hansen J A 
Published: January 2023

Abstract
The HLA class I gene family in lymphoblastoid cell line 721 has been studied in detail and a number of sequences in addition to the classical genes have been identified. The cloning, characterization, and nucleotide sequences of four sequences, all full length HLA class I pseudogenes, are described in this report. These pseudogenes, contained within 5.4-, 5.9-, 7.0-, and 9.2-kb HindIII fragments, each have the class I exon-intron structure as well as class I homology in their 5' and 3' flanking regions. However, all four sequences have one or more substitutions that perturb the coding region, leaving little doubt that they are in fact pseudogenes. Comparisons among these sequences and the HLA class I genes revealed that their homology with the class I genes is patchwork. Thus, although some regions have diverged, other contiguous intron-exon sequences are highly conserved. Comparisons in the 5' regions indicate that the pseudogene promoters more closely resemble the classical HLA promoters than the nonclassical promoters as none of the unique structural features found in the HLA-E, -F, or -G regulatory regions are present in any of the pseudogene promoters. Further comparisons revealed that at least two putative gene conversion events, similar to those hypothesized to have occurred in the evolution of some HLA genes, may have occurred in the evolution of some of the pseudogenes. These and other hypothetical events in the evolution of the class I gene family are discussed.
Mapping of an inducible element in the T cell receptor V beta 2 promoter.
Authors: Messier H , Ratanavongsiri J , Fuller T , Mangal S , Kilgannon P , Fotedar R , Fotedar A 
Published: January 2023

Abstract
The murine V beta 2 promoter was analyzed for an element regulating phorbol ester inducibility of the TCR beta chain gene. In transient expression analysis of 5' nested deleted fragments of the V beta 2 promoter, the TPA-inducible element mapped between -85 and -42. The -85 to -62 oligo conferred 12-0-tetradecanoylphorbol-13-acetate (TPA) inducibility to the heterologous TPA-uninducible thymidine kinase promoter. The -85 to -62 region contained an AP-1 site (-85 to -72) and inverted repeat motif (-72 to -62). The AP-1 site required the 3' flanking inverted repeat region for conferring optimal inducibility. In vitro transcribed and translated jun/fos heterodimers bind to the V beta 2 AP-1 motif with a 16-fold lower affinity as compared to the collagenase AP-1 motif. This explains the inability of the V beta 2 AP-1 motif to confer optimal TPA inducibility by itself. The affinity of jun/fos heterodimers for the V beta 2 AP-1 motif was not increased by the presence in cis of the inverted repeat motif. The 3' flanking inverted repeat binds the ets transactivator but not jun/fos heterodimers. The demonstrated cooperativity between the AP-1 and the 3' flanking sequence to confer TPA inducibility can thus be explained by the individual contributions of jun/fos and ets transactivators.
IFN-gamma and 1,25(OH)2D3 induce on THP-1 cells distinct patterns of cell surface antigen expression, cytokine production, and responsiveness to contact with activated T cells.
Authors: Vey E , Zhang J H , Dayer J M 
Published: January 2023

Abstract
Differentiation and maturation of monocytes are accompanied by the expression of specific surface glycoproteins, the secretion of cytokines, and the capacity to respond to ligands. These changes may be influenced by interactions with hormones, soluble lymphocytic products, or direct contact with lymphocytes. We have studied two distinct pathways in the differentiation of a human monocytic cell line, THP-1: one being induced by IFN-gamma and the other by 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). In THP-1 cells, IFN-gamma induces cell surface expression of HLA-DR and CD54 and production of IL-1 beta, TNF-alpha, and IL-6. In contrast, 1,25(OH)2D3 increases cell surface expression of CD11b and CD14, but fails to stimulate cytokine production. Direct contact of THP-1 with stimulated fixed T cells markedly induces IL-1 beta, TNF-alpha, and IL-6 production by THP-1. Production is higher when THP-1 have been previously exposed to 1,25(OH)2D3 as compared to prior exposure to IFN-gamma. mAb raised against certain relevant cell surface glycoproteins on THP-1 were tested for their ability to block the response of THP-1 to T cells. Antibodies to CD11a, CD11b, and CD11c, alone or in combination, only partially blocked IL-1 beta production by THP-1, whereas antibodies to CD54 and CD14 did not. Thus other unknown structures on the THP-1 cells may be involved in the induction of THP-1 cytokine production by T cell contact.
Decay-accelerating factor expression on either effector or target cells inhibits cytotoxicity by human natural killer cells.
Authors: Finberg R W , White W , Nicholson-Weller A 
Published: January 2023

Abstract
Previous studies have shown that freshly isolated CD16+ NK cells are deficient in the expression of decay-accelerating factor (DAF), or CD55, a membrane regulator of C3 activation. In this study we investigated the significance, for NK cell-mediated lysis, of DAF expression on the target and effector cells. The effect of DAF expression on the susceptibility of NK cell targets was investigated by several means: first, DAF- cell lines were cloned from K562; second, the cloned DAF- cells were reconstituted with exogenous purified DAF; and third, anti-DAF F(ab')2 was used to block DAF function on the DAF+ K562 cells. Consistently, the presence of DAF in the target cell membrane, either naturally occurring or experimentally incorporated, afforded the target cell protection against lysis, and this protection could be blocked with anti-DAF. Similarly, targets for antibody-dependent cell-mediated cytotoxicity with exogenous DAF incorporated in their plasma membrane became less sensitive to antibody-dependent cell-mediated cytotoxicity by NK cells compared with the same target cells without incorporated DAF in their membranes. DAF incorporated in the plasma membranes of the effector NK cells made the NK cells less effective at killing K562 targets. The known function of DAF is to regulate C3 activation, and we were able to demonstrate that the isolated NK cell is capable of releasing C3. It is also possible that the participation of DAF in NK cell function represents a new, noncomplement-dependent function for DAF.
In vivo activity of tumor necrosis factor (TNF) mutants. Secretory but not membrane-bound TNF mediates the regression of retrovirally transduced murine tumor.
Authors: Karp S E , Hwu P , Farber A , Restifo N P , Kriegler M , Mulé J J , Rosenberg S A 
Published: January 2023

Abstract
We have previously demonstrated that murine tumor cells transduced with a retrovirus containing the cDNA encoding wild-type human TNF regress in vivo when injected into immunocompetent mice; this regression is T cell mediated. To determine whether membrane-associated or secreted TNF was responsible for tumor regression, we transduced a cloned murine fibrosarcoma 205 F4 with retroviruses encoding modified human TNF genes. The cloned tumor lines of one retroviral transduction expressed only membrane bound 26-kDa TNF. This TNF could not be cleaved or secreted, but was present on the cell surface. A second retrovirus caused the expression of only secretory 17-kDa TNF, as the transmembrane domain of the cDNA was deleted. The TNF produced by tumor cells transduced with either retroviral vector was functional in vitro as direct lysis of the TNF-sensitive target L929 by transduced tumor cells was demonstrated. The TNF present on 26-kDa expressing tumors was membrane bound as supernatants from cultured 17-kDa TNF expressing tumor cells but not 26-kDa TNF expressing tumors mediated the lysis of L929 cells. Both tumors were injected s.c. into syngeneic mice and tumor growth was measured serially. In repeated experiments, 26-kDa TNF expressing tumors grew progressively in all mice. In contrast, 17-kDa TNF expressing tumors grew for 10 days and then regressed with all animals free of tumor at 28 days. Tumor regression was abrogated by in vivo injection of an anti-TNF antibody. Similar results were obtained in a second tumor model, 203 E4. Thus regression of TNF transduced tumors in vivo requires secretion of TNF, as membrane-bound TNF is insufficient to elicit the host response.
Selective suppressive effects of Trypanosoma cruzi infection on IL-2, c-myc, and c-fos gene expression.
Authors: Soong L , Tarleton R L 
Published: January 2023

Abstract
Infection with Trypanosoma cruzi is accompanied by a profound suppression of immune responses including the production of IL-2. Previous experiments have confirmed a correlated decrease in IL-2 mRNA levels in lymphoid cells from infected mice. To further define the molecular basis of this regulation, we have examined the production and degradation of mRNA for IL-2 and other T cell activation genes in cells from T. cruzi-infected mice. Spleen cells from C57BL/6J mice infected with the Brazil strain of T. cruzi were analyzed for the kinetic expression of IL-2, IL-2R alpha, c-myc, and c-fos genes in response to Con A and PMA costimulation. Cells from infected mice exhibited a selective reduction of c-myc and c-fos mRNA in association with the severe suppression of the IL-2 gene, but a less severe to comparable production of IL-2R alpha mRNA compared with normal spleen cells. The similar patterns of the suppression of c-myc and IL-2 mRNA suggest a common mechanism of down-regulation of these two genes in T. cruzi infection. Actinomycin D treatment was used to demonstrate that decreased steady state levels of IL-2, c-myc, and c-fos mRNA in cells from infected mice were not due to an increased rate of degradation of these mRNA. Cycloheximide treatment enhanced the expression of IL-2, IL-2R alpha, c-myc, and c-fos mRNA in spleen cells from both normal and infected mice. Although a larger percentage of induction was observed in cells from infected mice, the mRNA levels for IL-2, c-myc, and c-fos in cells from infected mice were still lower than those of normal cells. Spleen cells from infected mice precultured for 24 to 72 h before the addition of mitogens showed significant enhancement of IL-2 and c-myc gene expression; however, this recovery was inhibited if fixed T. cruzi was present in the preculture medium. These data suggest that the reduction of IL-2 mRNA in infected mice is not the result of an increased degradation of its mRNA but to down-regulation of transcription of the IL-2 gene in T cells from T. cruzi-infected mice. Preculture-induced recovery of IL-2 production appears to result from release from this regulation and full expression of the IL-2 gene.
Expression of CD7 on normal human myeloid progenitors.
Authors: Chabannon C , Wood P , Torok-Storb B 
Published: January 2023

Abstract
Existence of biphenotypic leukemias co-expressing CD7 and CD34 has prompted the question of whether a similar population of cells is present in normal human bone marrow. As CD7 is considered to be a T cell-restricted Ag, the co-expression of CD7 with the "human stem cell Ag" CD34 may identify a bipotent stage within hemopoietic differentiation. Cells with this phenotype have previously been isolated from human thymus. In this report we provide evidence that human marrow mononuclear cells also contain a minor subpopulation of cells co-expressing CD7 and CD34. The CD7+/CD34+ cells were found to contain committed myeloid progenitors assayed both as CFU in semi-solid media and by their ability to produce granulocytes in long term marrow cultures. Expression of CD7 on myeloid committed progenitors was further confirmed in a C-mediated cytotoxic assay. We conclude that CD7 expression is not restricted to T cells but is also expressed during early stages of myeloid differentiation.
In vitro inhibitory effect of IL-8 and other chemoattractants on neutrophil-endothelial adhesive interactions.
Authors: Luscinskas F W , Kiely J M , Ding H , Obin M S , Hébert C A , Baker J B , Gimbrone M A 
Published: January 2023

Abstract
We have previously reported that cytokine- or LPS-activated human umbilical vein endothelial cell (HUVEC) monolayers secrete IL-8 that can act as a neutrophil-selective adhesion inhibitor. In our study we investigated the mechanisms involved in the leukocyte adhesion inhibitory action of IL-8. The leukocyte adhesion inhibitory effect appears to be mediated by the action of IL-8 on the neutrophil, does not involve down-regulation of relevant endothelial adhesion molecules such as endothelial-leukocyte adhesion molecule-1 or intercellular adhesion molecule-1, and is quantitatively similar in different endothelial activation states that are predominantly endothelial-leukocyte adhesion molecule-1 dependent or intercellular adhesion molecule-1 dependent. In addition to inhibiting the attachment of freshly isolated peripheral blood neutrophils to cytokine-activated HUVEC monolayers, IL-8 also promoted a rapid detachment of tightly adherent neutrophils from activated HUVEC, and abolished neutrophil transendothelial migration. Certain other chemoattractants, including FMLP and C5a, had similar inhibitory actions, indicating IL-8 was not unique in its ability to inhibit various neutrophil-endothelial interactions. In contrast, two other neutrophil agonists 1-0-alkyl-2-acetyl sn-glycero-3-phosphocholine and granulocyte-macrophage-CSF, which, like IL-8, are produced by activated HUVEC, as well as the leukocyte-derived chemoattractant leukotriene B4, exerted minimal inhibitory effects on adhesion. Regardless of their ability to modulate neutrophil-endothelial cell adhesion, all these agents induced altered leukocyte surface expression of functionally important adhesion molecules, including loss of L-selectin (leukocyte adhesion molecule-1, LECAM-1) and increase in CD11b/CD18. Thus, although the above agonists have been characterized primarily as chemoattractants, our findings demonstrate that these agents can exert a wide range of modulatory effects on neutrophil-endothelial adhesive interactions.