bluuebunny/crossref_metadata_2025_split huggingface dataset:
cAMP and human neutrophil chemotaxis. Elevation of cAMP differentially affects chemotactic responsiveness.
Authors: Harvath L , Robbins J D , Russell A A , Seamon K B 
Published: December 2022

Abstract
Neutrophils (PMN) treated with cAMP elevating agents were evaluated for their chemotactic responsiveness to FMLP and leukotriene B4 (LTB4). PGE1 and isoproterenol, increased PMN cyclic AMP production and inhibited chemotaxis to both FMLP and LTB4. In contrast, forskolin, which activates adenylate cyclase directly, inhibited chemotaxis to FMLP but not to LTB4. The phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), was required for inhibition of PMN chemotaxis to FMLP by forskolin, PGE1, and isoproterenol. Isoproterenol and PGE1 inhibited PMN chemotaxis to LTB4 in the absence of IBMX and chemotaxis was further inhibited in the presence of IBMX. PMN cAMP levels were stimulated 2- to 3-fold with isoproterenol, 6- to 10-fold with PGE1, and 5- to 7-fold with forskolin over basal levels in the presence of IBMX. These observations demonstrate that total cellular cAMP concentration is not correlated with inhibition of PMN chemotaxis to all stimuli; forskolin, which increased cyclic AMP 5- to 7-fold over basal levels, did not inhibit chemotaxis to LTB4, whereas isoproterenol, which increased cyclic AMP only 2- to 3-fold over basal levels, inhibited chemotaxis to LTB4. PMN cAMP extrusion was determined under basal conditions and in the presence of PGE1, isoproterenol, or forskolin. PMN extruded cAMP under all conditions examined.
Recombinant soluble human complement receptor type 1 inhibits inflammation in the reversed passive arthus reaction in rats.
Authors: Yeh C G , Marsh H C , Carson G R , Berman L , Concino M F , Scesney S M , Kuestner R E , Skibbens R , Donahue K A , Ip S H 
Published: December 2022

Abstract
The human CR1 was genetically engineered by site directed mutagenesis into a truncated form which was secreted from transfected Chinese hamster ovary cells. This soluble recombinant CR1 (sCR1) was purified from the supernatants of the Chinese hamster ovary cells cultured in a hollow fiber bioreactor. sCR1 inhibits the C3 and C5 convertases of the classical and the alternative pathways in vitro. The ability of sCR1 to inhibit the immune complex-mediated inflammation in vivo was tested in a rat reversed passive Arthus reaction model. Administration of sCR1 at the dermal sites reduced the Arthus vasculitis in a dose-dependent manner as judged by both gross and microscopic examination, as well as by immunohistologic localization of C3 and C5b-9 neoantigen deposits. These data suggest that sCR1 inhibits the Arthus reaction by interrupting the activation of the C cascade, hence limiting the detrimental immune complex-induced tissue damage in vivo.
Two roles for CD4 cells in the control of the generation of cytotoxic T lymphocytes.
Authors: Cassell D , Forman J 
Published: December 2022

Abstract
The generation of CTL against Qa-1 Ag in C57BL/6 (B6) (Qa-1b) and B6.Tlaa (Qa-1a) congenic strains requires in vivo priming with the Qa-1 alloantigen together with a helper Ag, such as H-Y. The primed precursors obtained from these female mice generate Qa-1-specific CTL activity upon culture in vitro. Although the presence of the H-Y helper Ag is not required for the in vitro sensitization, no response occurs in the absence of CD4 cells. Addition of unprimed B6.Tlaa CD4 cells from Qa-1 incompatible radiation bone marrow chimeras (B6.Tlaa----B6), that are presumably tolerant to Qa-1b, provide helper activity for Qa-1b-specific CTL. This indicates that although CD4 cells are obligatory for the Qa-1 response, they need not be specific for alloantigens on the APC to generate helper activity in in vitro cultures. Addition of unirradiated B6 CD8-depleted spleen cells to CD4-depleted B6.Tlaa anti-B6 cultures in the presence of either B6.Tlaa CD4 cells or rIL-2 prevents the generation of Qa-1 specific CTL. This inhibition is not due to an anti-idiotypic Ts cell since B6.Tlaa----B6 chimeric cells do not suppress an anti-Qa-1b response. Rather, this finding is consistent with that of a veto cell mechanism. To determine whether CD4 cells themselves exhibit veto activity, highly purified CD4 populations were tested for their ability to inhibit the generation of Qa-1-specific CTL. CD4 cells precultured for 2 to 3 days with Con A and rIL-2 specifically inhibit CTL activity whereas resting cells do not, similar to that noted for CD8 veto cells. The relative efficiency of activated CD4 cells is greater than that of resting NK cells but is less than that of activated CD8 or NK cells. Thus, CD4 cells not only provide helper activity for CTL precursors, but also act as veto cells to prevent the generation of CTL activity.
The primary B cell response to the O/core region of bacterial lipopolysaccharide is restricted to the Ly-1 lineage.
Authors: Su S D , Ward M M , Apicella M A , Ward R E 
Published: December 2022

Abstract
Experiments were performed to test the hypothesis that Ly-1 B cells respond to antigenic challenge with LPS from gram-negative bacteria. To perform these experiments, the splenic fragment culture system for the study of B cell precursors was used. We found that a significant number of anti-O/core, but not anti-lipid A, precursors expressed the lambda L chain. A restriction of the anti-LPS response to Ly-1 B cells was tested using a Ly-1 depletion protocol. We found that the anti-O/core antibody response was restricted to the Ly-1 B cell lineage. In contrast, conventional B cells, not Ly-1 B cells, respond to an antigenic challenge with lipid A. Our results further support the idea that the Ly-1 B cell lineage serves a direct role in protecting against certain bacterial infections.
Structure of the mouse beta Fc gamma receptor II gene.
Authors: Hogarth P M , Witort E , Hulett M D , Bonnerot C , Even J , Fridman W H , McKenzie I F 
Published: December 2022

Abstract
We have isolated and deduced the structure of the beta Fc gamma RII gene from the mouse. This gene spans approximately 18 kb of DNA; the structure and nucleotide sequence has been determined and potential regulatory sites identified. This gene is composed of 10 exons that give rise to the beta 1 and beta 2 Fc gamma RII cDNA. Four exons encode the 5' untranslated region and leader sequence, one exon for each Ig-binding domain and membrane-spanning region and three exons encoding the cytoplasmic tail and 3' untranslated region. Analysis of the gene structure indicated that the beta 1Fc gamma RII and beta 2Fc gamma RII arise by differential mRNA splicing when a single 141-bp exon (exon 8) is alternately spliced to give rise to these isoforms. Sequence analysis of 2 kbp upstream of the transcription start site indicated the presence of regulatory elements, including three binding sites for the transcription factor Sp1, and Ap-4 binding site, a tandem glucocorticoid response element, and an overlapping tandem repeat. Furthermore, as in the Thy-1 gene, no CAT or TATA consensus sequences were observed. In addition, sites of methylation that regulate expression of this gene were also located at the 5' end of the gene and within several introns. A large intron located between exons 4 and 5 also contained a series of purine/pyrimidine-rich regions and a potential enhancer sequence.
Activation of human CD4 T lymphocytes. Interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor.
Authors: Yamada A , Nikaido T , Nojima Y , Schlossman S F , Morimoto C 
Published: December 2022

Abstract
Fibronectin synergized with anti-CD3 antibody to promote CD4 cell proliferation in a serum-free culture system whereas no proliferation was observed when CD4 cells were cultured with anti-CD3 alone or fibronectin alone. In addition, anti-CD29 (integrin beta 1) as well as anti-VLA-5 (human fibronectin receptor) antibodies blocked this CD4 cell activation in this system. Although anti-CD3 alone or fibronectin alone cannot induce IL-2 message by CD4 cells, the combination of anti-CD3 plus fibronectin induced IL-2 message by CD4 cells. In an analysis of the molecular mechanism by which IL-2 message was generated, we showed that a fibronectin-VLA-5 fibronectin receptor interaction may contribute an independent signal distinct from the CD3 pathway of activation by the induction of an AP-1 transcriptional factor. Thus the VLA-5 fibronectin receptor on CD4 cells can play a complementary role in CD3-TCR-mediated signal transduction through its interaction with fibronectin.
B cell activation during HIV-1 infection. II. Cell-to-cell interactions and cytokine requirement.
Authors: Amadori A , Zamarchi R , Veronese M L , Panozzo M , Barelli A , Borri A , Sironi M , Colotta F , Mantovani A , Chieco-Bianchi L 
Published: December 2022

Abstract
This study examined the mechanisms underlying the intense activation of HIV-1-specific B cells observed in peripheral blood of HIV-1-infected subjects. Spontaneous in vitro synthesis of anti-HIV-1 antibodies, as well as total Ig production, were dramatically reduced by accessory cell, but not T cell removal. This fall was counteracted by addition of rIL-6, but not other cytokines, to monocyte-depleted cultures; moreover, antisera against IL-6 suppressed spontaneous anti-HIV-1 antibody synthesis in a dose-dependent manner. Although IL-6 apparently sustained HIV-1-specific B cell activation, no increase in serum IL-6 levels was observed; PBMC from seropositive subjects did not produce increased amounts of IL-6 in vitro, compared to seronegative controls, both spontaneously and in the presence of LPS stimulation; finally, no constitutive expression of IL-6 gene could be documented in freshly isolated PBMC. These findings indicate that IL-6 may play a central role in HIV-1-specific B cell activation in seropositive patients, and further stress the importance of this cytokine during HIV-1 infection.
IgE-dependent cytokine production by human peripheral blood mononuclear phagocytes.
Authors: Borish L , Mascali J J , Rosenwasser L J 
Published: December 2022

Abstract
These studies demonstrate the IgE-dependent production of IL-1 beta and TNF-alpha by circulating blood monocytes. IL-1 beta production was demonstrated biologically as the stimulation of proliferation of the cloned IL-1-dependent murine T cell line D10.G4.1 in the presence of a submitogenic concentration of PHA. In a representative experiment, 3H-thymidine uptake increased from 57826 cpm in the presence of supernatants obtained from unstimulated cells to 200774 cpm with supernatants from monocytes stimulated by IgE/alpha IgE immune complexes. By ELISA, IgE complexes increased IL-1 beta production from 0.54 +/- 0.06 ng (per 10(6) monocytes) to 2.60 +/- 0.62 ng (p less than 0.01; mean of eight experiments) and TNF-alpha production from 0.17 +/- 0.10 ng to 3.00 +/- 0.54 ng (p less than 0.01; mean of four experiments). No IL-1 alpha secretion was observed. RNA hybridization analysis demonstrated that IL-1 beta production represented de novo synthesis of the cytokine. Stimulated RNA production was observed after a minimal 1/2-h incubation and was maximal at 2 h. The IgE-dependent secretion of these pro-inflammatory cytokines by mononuclear phagocytic cells may contribute to the inflammation characteristic of allergic responses.
Characterization of a new, potent, immunopathogenic epitope in S-antigen that elicits T cells expressing V beta 8 and V alpha 2-like genes.
Authors: Merryman C F , Donoso L A , Zhang X M , Heber-Katz E , Gregerson D S 
Published: December 2022

Abstract
Experimental autoimmune uveoretinitis (EAU) is a predominantly T cell-mediated autoimmune disease induced in susceptible animals by active immunization with human or bovine retinal S-Ag or by passive transfer of activated S-Ag or peptide-specific CD4+ T cells. During the course of studies aimed at the identification of T cell and B cell recognition sites in bovine and human S-Ag, a new potent uveitogenic region, located near the carboxy terminus of the molecule, was identified and characterized. Analysis of several synthetic peptides from this region showed that a 14 amino acid residue peptide, BSAg339-352, was highly uveitogenic when injected with adjuvants into Lewis rats. A uveitogenic T cell line, R737, was raised by in vitro selection of lymphocytes from animals immunized with peptide BSAg333-352. Northern blot analysis of mRNA from the R737 T cell line was positive for the rat homologs of murine V beta 8 and V alpha 2 T cell receptor gene probes. Whereas peptide BSAg339-352 defined the pathogenic site, nonpathogenic, proliferative sites were found in close physical association. This region is immediately adjacent to previously characterized pathogenic and proliferative sites contained in residues BSAg352-364. These results, as well as our previous observations, show S-Ag to be a complex molecule with several highly conserved amino acid sequences that can elicit pathogenic T cells with restricted T cell receptor V gene usage capable of active and passive elicitation of experimental autoimmune uveoretinitis.
Analysis of protein phosphorylation patterns reveals unanticipated complexity in T lymphocyte activation pathways.
Authors: Patel H R , Miller R A 
Published: December 2022

Abstract
Protein kinases are considered likely to play important roles in the still dimly understood process by which mitogens induce resting T lymphocytes to enter the cell cycle. Using two-dimensional electrophoretic analysis of lysates from orthophosphate-labeled cells, we have compared patterns of phosphorylation in freshly isolated murine splenic T cells exposed to three mitogenic agents: antibody to the epsilon-chain of the TCR CD3 complex, the plant lectin Con A, and a mixture of PMA and ionomycin, which together bypass the signal transduction apparatus to activate intracellular pathways. Of 14 phosphoproteins found whose level of phosphorylation was increased (at least fivefold) by anti-CD3 epsilon antibody, 13 also responded to the mixture of PMA and ionomycin. Surprisingly, however, only 5 of these 14 also responded strongly to Con A exposure. We also identified two substrates that were phosphorylated in response to Con A but not to anti-CD3. Phosphorylation patterns were also studied in T cells exposed to either PMA or ionomycin alone, to gain further insight into the role of protein kinase C and calcium-dependent events in the activation process. Of 16 phosphoproteins that responded to mixtures of PMA and ionomycin, 4 were shown to require the ionomycin signal, 2 to require the PMA signal, and 3 others to respond only when both activators were present; the other 7 responded to either agonist added alone. In addition, we found two PMA-sensitive phosphoproteins in which phosphorylation was inhibited by ionomycin induced calcium signals. Finally, we identified several phosphoproteins which show differential responsiveness in CD4+ and CD8+ T cells. Classification of kinase substrates based on their differential susceptibility to these stimuli should provide new insights into the mode of action of agents and diseases that affect T cell activation.
Epidermal Langerhans cells are not principal reservoirs of virus in HIV disease.
Authors: Kalter D C , Greenhouse J J , Orenstein J M , Schnittman S M , Gendelman H E , Meltzer M S 
Published: December 2022

Abstract
Several reports implicate Langerhans cells of skin as susceptible targets, reservoirs, and vectors for transmission of HIV: 1) numbers of Langerhans cells in skin of HIV-infected patients were decreased about 50% of that in control skin; 2) as many as 30% of Langerhans cells in the skin of HIV-infected patients were morphologically abnormal; 3) viral particles typical for HIV were identified in or around 2 to 5% of these cells; and 4) infectious HIV was isolated from skin biopsies of infected patients. These results were consistent with similar observations of HIV-infected macrophages in such tissues as brain, lung, and lymph node. Despite these findings, other investigators find no evidence for virus infection in the epidermis of HIV-infected patients by any of several immunohistochemical or ultrastructural criteria. To address this controversy, we obtained skin from 28 HIV-seropositive subjects at various clinical stages by full thickness biopsy or suction blister. Samples were analyzed by transmission electron microscopy for presence of HIV virions, by immunofluorescent staining for viral proteins, by in situ hybridization for HIV-specific mRNA, by polymerase chain reaction amplification of virus-specific DNA, and by direct virus isolation by coculture of epidermis onto monocyte target cells. By any of these techniques, demonstration of HIV in the epidermis of infected patients was equivocal and even then, infrequent. In contrast, viral DNA was detected from the dermis of the same skin samples (26 of 28 samples). Moreover, the number and morphology of Langerhans cells in skin of infected patients were within normal limits, regardless of stage of disease. These studies in toto suggest that a role for Langerhans cells as a principal viral reservoir or vector of transmission is highly unlikely.
Inflammatory edema induced by interactions between IL-1 and the neuropeptide calcitonin gene-related peptide.
Authors: Buckley T L , Brain S D , Collins P D , Williams T J 
Published: December 2022

Abstract
The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator with a long duration of action. CGRP is widely distributed and is present in perivascular nerves of tissues that include skin and the synovium. In this study we have investigated the possibility that CGRP can modulate the inflammatory actions of the cytokine IL-1 by using an inflammatory model in rabbit skin. The intradermal injection of IL-1 (1.4 x 10(-14) mol/site) alone stimulated little edema formation. However, when IL-1 was injected with CGRP (10(-11) mol/site), a highly significant edema was observed, and neutrophil accumulation induced by IL-1 was potentiated. These results suggest that the action of IL-1 as a potent mediator of increased microvascular permeability is only observed when skin blood flow is increased in this model. This was confirmed by experiments in which PGE2 (3 x 10(-9) mol/site) at a dose with a similar duration of vasodilator action as CGRP (10(-11) mol/site) also potentiated edema induced by IL-1. Further experiments investigated the mechanism by which IL-1 increased microvascular permeability. Edema induced by IL-1 was dependent on de novo protein synthesis and the presence of circulating neutrophils. However, selective platelet-activating factor and histamine H1 antagonists had no inhibitory effect on this response. Thus it appears that when a microvascular bed is dilated by the long-lasting vasodilator CGRP, edema induced by IL-1 is clearly observed. These results highlight a potentially important synergistic interaction between cytokines and neuropeptides in inflammation.
IL-6 and tumor necrosis factor-alpha. Autocrine and paracrine cytokines involved in B cell function.
Authors: Rieckmann P , D'Alessandro F , Nordan R P , Fauci A S , Kehrl J H 
Published: December 2022

Abstract
IL-6 and TNF-alpha are synthesized and secreted by normal tonsillar B cells after stimulation with the polyclonal B cell activator Staphylococcus aureus Cowan strain 1 (SAC) and IL-2 as well as spontaneously by in vivo activated B cells from patients with hypergammaglobulinemia. Using specific neutralizing antibodies, both factors were shown to be involved in autocrine and/or paracrine regulation of B cell differentiation. IgG induced by SAC/IL-2 stimulation was reduced 73% with an anti-IL-6 antibody and 40% with an anti-TNF-alpha antibody. Similar effects of these antibodies were observed on the spontaneous in vitro IgG production by lymphoblastic B cells from six patients with hypergammaglobulinemia. Kinetic studies with SAC/IL-2-activated B cells revealed that the anti-TNF-alpha antibody must be present at the beginning of the culture to exert an effect on Ig production, whereas the anti-IL-6 antibody reduced Ig production even if added as late as day 3. This sequential action of TNF-alpha and IL-6 on B cell differentiation was reflected by different kinetics of release of these two cytokines into the supernatant of SAC/IL-2 activated B cells; TNF-alpha peaked at 24 h and IL-6 at 96 h after stimulation. In addition, it was shown that IL-6 production by in vitro-activated B cells was partially blocked by an anti-TNF-alpha antibody suggesting that TNF-alpha regulates IL-6 production in normal B cells via an autocrine pathway. We also investigated the effects of TGF-beta on TNF-alpha and IL-6 production by normal B cells. Although TGF-beta inhibited Ig production by in vitro-activated and in vivo-activated B cells, it did not inhibit the release of these cytokines from normal B cells. Furthermore, TGF-beta did not inhibit the induction of nuclear factor-IL-6 nor the expression of IL-6R on activated B cells. Thus, although the biologic effects of anti-IL-6 and TGF-beta on B cell Ig production are similar, their mechanisms of actions appear to be distinct.
Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B.
Authors: Abe J , Forrester J , Nakahara T , Lafferty J A , Kotzin B L , Leung D Y 
Published: December 2022

Abstract
Streptococcal exotoxins have been implicated in the pathogenesis of a toxic shock-like syndrome and scarlet fever. Previous studies have demonstrated that these toxins are potent stimulators of human T cells and have structural homology to staphylococcal enterotoxins. In the current study, we investigated the mechanism by which streptococcal erythrogenic toxins type A (SPEA) and B (SPEB) activate T cells and compared it with anti-CD3 and the known "superantigen" staphylococcal enterotoxin B. SPEA was found to selectively activate T cells bearing V beta 8, V beta 12, and V beta 14, whereas SPEB selectively activated T cells bearing V beta 2 and V beta 8. Furthermore, fibroblasts transfected with MHC class II molecules were capable of presenting SPEA and SPEB to purified T cells. The T cell response to these toxins, however, was not MHC-restricted. Although the streptococcal exotoxins stimulated both CD4+ and CD8+ T cells, SPEA but not SPEB stimulated the CD4+ T cell subset proportionately more than the CD8+ T cell subset. Our results indicate that SPEA and SPEB, like the staphylococcal enterotoxins, are superantigens and suggest a mechanism by which they may mediate particular systemic syndromes associated with streptococcal infections.