bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine activates A2 receptors to inhibit neutrophil adhesion and injury to isolated cardiac myocytes.
Authors: Bullough D A , Magill M J , Firestein G S , Mullane K M 
Published: December 2022

Abstract
Inhibition of neutrophil-myocyte adhesion and adhesion-dependent myocyte injury by adenosine was evaluated using isolated TNF-alpha-activated canine cells. Adenosine inhibited adhesion of activated neutrophils to cardiac myocytes with an IC50 of 11 +/- 4 nM. Inhibition of neutrophil adhesion (92 +/-3% by 100 nM adenosine) led to inhibition of myocyte injury (by 90 +/- 6%, as assessed by dye exclusion). Inhibition of cell adhesion by adenosine was blocked by the A2 antagonist, 1,3-dimethyl-1-propylxanthine, but not by the A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine. Moreover, the A2 agonist, CGS21680 (2-[4-(2-carboxymethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine), but not the A1 agonist, N6-cyclopentyladenosine, mimicked adenosine in preventing cell adhesion. These observations implicate the A2 receptor in the mechanism of inhibition of cell adhesion. pretreatment and washing of neutrophils, but not cardiac myocytes, with adenosine or CGS21680 led to inhibition of adhesion, suggesting that the neutrophil A2 receptor is the target of adenosine's action. In contrast, inhibition of cell adhesion by adenosine was poteniated by 8-cyclopentyl-1,3-dipropylxanthine (IC50 = 4 +/- 1 nM) and attenuated by N6-cyclopentyladenosine, suggesting that occupancy of A1 receptors can conversely increase cell adhesion. Neutrophil-myocyte adhesion was inhibited by acadesine (IC50 = 12 +/- 2 microM) also via an adenosine-dependent mechanism because it was blocked by 1,3-dimethyl-1-propylxanthine or adenosine deaminase, an enzyme that degrades any adenosine that is formed. Acadesine-induced inhibition if cell adhesion (83 +/- 4% by 100 microM) resulted in inhibition of myocyte injury (by 76 +/- 6%). Other adenosine-regulating agents, including the acadesine analogue, GP531 (5-amino-1 beta-D-(5-benzylamino-5-deoxyribofuranosyl) imidazole-4-carboxamide), and inhibitors of adenosine transport and intracellular metabolism also inhibited cell adhesion. These results indicate that exogenous or endogenous adenosine can inhibit neutrophil-myocyte adhesion and injury in cells activated with TNF-alpha by an A2-mediated mechanism. Although the predominant activity of adenosine is to attenuate cell adhesion, stimulation of A1 receptors has the opposite effect, i.e., to augment adhesive interactions.
Regulation of the expression of IL-8 receptor A/B by IL-8: possible functions of each receptor.
Authors: Chuntharapai A , Kim K J 
Published: December 2022

Abstract
We investigated the regulatory mechanism of the expression of IL-8R, IL-8R type A (IL-8RA), and IL-8R type B (IL-8RB) on human neutrophils by IL-8. The expression of IL-8RA/B was analyzed by flow cytometry using mAb specific for each receptor. IL-8 down-modulated &gt; 90% of IL-8RA and IL-8RB expression within 5 min. A related C-X-C chemokine, melamona growth stimulatory activity, down-modulated IL-8RB but not IL-8RA. It required 7 to 13 times more IL-8 to down-modulate IL-8RA than IL-8RB, as determined by the half-maximal effective concentration of IL-8. Scatchard analysis showed that the affinity of IL-8RA for IL-8 was lower than that of IL-8RB. The possible functions of each IL-8R were explored by comparing 1) the expression levels of IL-8RA/B on migrated neutrophils during in vitro chemotaxis assay and 2) the recovery rate of IL-8RA/B expression after down-modulation by IL-8. Results obtained from the in vitro chemotaxis show that the expression level of IL-8RB, but not IL-8RA, on neutrophils that migrated into the chamber containing low concentrations (&lt; 1 nM) of IL-8 was significantly reduced compared with the control level. This suggests that IL-8RB may play as active role in the initiation of neutrophil migration distant from the site of inflammation, where the concentration of IL-8 is at the picomolar level. After down-modulation by 119 nM IL-8, the expression of IL-8RA fully recovered within 1.5 h, while the recovery rate of IL-8RB expression was slow and never reached more than 40% of the control level during a 3-h culture period. The rapid reexpression of IL-8RA suggests that the low affinity IL-8RA may play a more active role in mediating IL-8 signal at the site of inflammation, where the concentration of IL-8 is high.
A link between catalytic activity, IgE-independent mast cell activation, and allergenicity of bee venom phospholipase A2.
Authors: Dudler T , Machado D C , Kolbe L , Annand R R , Rhodes N , Gelb M H , Koelsch K , Suter M , Helm B A 
Published: December 2022

Abstract
The molecular and cellular mechanisms controlling Ab isotype selection following encounter of a given Ag are still unclear, although the regulatory role of cytokines is established. In the present study we explored the possibility that the nonimmunologic interaction of an allergen with cells of the innate immune system might result in a release of mediators that promote IgE isotype selection in adaptive responses. Using the bee venom allergen phospholipase A2 (PLA2) and a mutant variant lacking enzymatic function, we show that PLA2, but not its catalytically inactive variant, is able to induce IgE-independent mediator release, including IL-4, from rodent mast cells. Assessing the in vivo relevance of these observations, we find that repeated injections of low doses of active enzyme into mice induce the synthesis of high levels of PLA2-specific IgE, while immunization with the inactive form yields no detectable IgE response. Both Ags were similarly immunogenic when high doses of Ag were used for immunization. These findings suggest that mast cells might be a source of IL-4 at the onset of specific immunity against sources of allergens such as bee venom that contain PLA2 and support the concept that the biologic action of an Ag on cells of the innate immune system can play a role in determining adaptive immune responses.
Exogenous hepatitis B surface antigen particles processed by dendritic cells or macrophages prime murine MHC class I-restricted cytotoxic T lymphocytes in vivo.
Authors: Böhm W , Schirmbeck R , Elbe A , Melber K , Diminky D , Kraal G , van Rooijen N , Barenholz Y , Reimann J 
Published: December 2022

Abstract
Injection of low doses of particulate hepatitis B surface Ag (HBsAg) into H-2d mice without adjuvants primes an Ld-restricted, S28-39-specific T cell response. This study indicates that dendritic cells (DC) and macrophages (M phi) both serve as APCs that support priming of CD8+ CTL precursors in vivo to exogenous HBsAg particles. After transfer into a syngeneic, naive host, HBsAg particle-pulsed DC, either freshly purified from skin or derived from a cloned DC line, efficiently primed class I-restricted, HBsAg-specific CTL precursors. M phi, either harvested from the peritoneal cavity or generated in macrophage-CSF-stimulated bone marrow cell cultures in vitro or derived from established, cloned M phi lines (PU5-1.8, J774A.1), pulsed with HBsAg particles in vivo or in vitro, elicited a class I-restricted, HBsAg-specific CTL response after adoptive transfer into naive hosts. The class I-restricted CTL response induced by HBsAg particle immunization was suppressed in carrageenan-treated mice, but was restored when carrageenan-treated mice were immunized with syngeneic, HBsAg-pulsed M phi. Selective elimination of M phi by liposome-incorporated dichloromethylene-diphosphonat did not suppress the induction of a CTL response of H-2d mice by HBsAg particle immunization. HBsAg-pulsed, freshly prepared DC are more potent than pulsed M phi in priming class I-restricted CTL in vivo. The relative importance of both types of APC in priming CTL remains to be resolved.
Estrogen suppresses stromal cell-dependent lymphopoiesis in culture.
Authors: Smithson G , Medina K , Ponting I , Kincade P W 
Published: December 2022

Abstract
Numbers of pre-B cells change dramatically and reciprocally in response to estrogen levels in mice, suggesting that normal lymphopoiesis may be under hormonal control. However, little is known of the mechanisms involved in this process. We found that estrogen receptor mRNA was detectable by RT-PCR in lymphocyte supporting stromal cells as well as B lymphocyte precursors. Unlike glucocorticoids, estrogen did not induce apoptosis in isolated B lineage lymphocytes or interfere with their responsiveness to IL-7 in semisolid agar. Estrogen did inhibit clonal expansion of B cell precursors in a limiting dilution-type assay when the lymphocytes were cultured on a stromal cell clone. In other experiments, B cell precursors at particular stages of differentiation were isolated by cell sorting and cocultured with stromal cells for 4 days. This revealed that some subsets were more sensitive to an estrogen-containing environment than others. Although numbers of recovered cells were greatly reduced, the remaining lymphocytes had undergone relatively normal differentiation. The surviving population was enriched in cells that had acquired cytoplasmic mu chains, BP-1 Ag, and clonability with IL-7. Hormone-mediated inhibition occurred in serum and phenol-red free medium, and in cultures replete with IL-7. Direct contact between stromal cells and lymphocytes was not required. Furthermore, suppression resulted when stromal cells alone were treated with the hormone. These findings indicate that estrogen may regulate B lymphopoiesis via its influence on the microenvironment and that estrogen-induced stromal cell genes merit further study.
IFN-gamma induces a p91/Stat1 alpha-related transcription factor with distinct activation and binding properties.
Authors: Guyer N B , Severns C W , Wong P , Feghali C A , Wright T M 
Published: December 2022

Abstract
The 5' flanking region of the mig gene, a member of the chemokine family of small m.w. chemoattractant and growth regulatory factors, contains an IFN-gamma-responsive enhancer, gamma RE-1, consisting of an extended imperfect palindrome. In this report we show that a novel factor, gamma RF-1, which binds to the gamma RE-1 element, is rapidly activated in a variety of primary cell types and tumor cell lines treated with IFN-gamma. Our data indicate that gamma RF-1 is present in a latent form in unstimulated cells and its DNA-binding activity is dependent upon tyrosine phosphorylation. UV cross-linking studies revealed that gamma RF-1 consists of at least two proteins of approximately 95 and 130 kDa, which interact with the gamma RE-1 element. A comparison of gamma RF-1 and GAF, an IFN-gamma-activated transcription factor containing the p91/Stat1 alpha protein (Stat, signal transducer and activator of transcription), showed that these two factors exhibited differences in electrophoretic mobility, responsiveness to IFN-alpha, and kinetics of activation. Using anti-Stat Ab, however, we found that one or more subunits of gamma RF-1 are antigenically related to p91/Stat1 alpha. Our results indicate, therefore, that gamma RF-1 and GAF are distinct IFN-gamma-responsive transcription factors and probably contain closely related members of the Stat protein family.
The actin-binding protein, lymphocyte-specific protein 1, is expressed in human leukocytes and human myeloid and lymphoid cell lines.
Authors: Li Y , Guerrero A , Howard T H 
Published: December 2022

Abstract
Lymphocyte-specific protein 1 (LSP1) was originally reported as a lymphocyte-specific actin-binding protein using murine LSP1 probes. Subsequently, we identified LSP1 in polymorphonuclear neutrophils (PMN) and showed that it is the overexpressed 47-kDa protein in neutrophil actin dysfunction with 47- and 89-kDa abnormalities. This suggests that regulation of LSP1 expression in myeloid cells may be a functionally important event. LSP1 expression in human leukocytes, lymphoid cell lines, and myeloid cell lines (PLB985, HL60, and U937), uninduced (U) or induced to granulocytic (GI) or monocytic (MI) differentiation, was analyzed by Northern blot and immunoblot. By immunoblot, LSP1 is strongly expressed in PMN, less expressed in lymphocytes and monocytes (30-40% and 55-65% of the PMN level, respectively). By immunoblot and Northern blot, LSP1 is minimally expressed in U-PLB985 and U-HL60 (&lt; 10% of the PMN level) and is weakly expressed in the B lymphoid cell line Daudi, but is not expressed in the pro-B, pre-B, T lymphoid cell lines tested, U-U937 or MI-U937. LSP1 mRNA and protein are up-regulated in GI-PLB985, GI-HL60, and MI-HL60. In HL60, LSP1 mRNA and protein increase in parallel to a maximum of eightfold the basal level on days 5 to 6 of granulocytic differentiation and four- to fivefold the basal level on day 3 of monocytic differentiation. The results show that LSP1 is expressed in all human leukocytes, and its expression is up-regulated during granulocytic and monocytic differentiation of myeloid cells in vitro. Since its overexpression is implicated in the functional pathogenesis of a novel human neutrophil motile dysfunction and microfilamentous cytoskeletal abnormality (NAD 47/89), finding LSP1 in all human leukocytes suggests that it plays a role in regulating microfilamentous cytoskeleton structure and motile function in all leukocytes. Since the protein is not lymphocyte specific and is an F-actin binding protein, and its isoforms are expressed in stromal and embryonic mesenchymal cells, we propose that the protein's name be changed to leufactin, as an abbreviated form of leukocyte F-actin binding protein.
Characterization of intercellular adhesion molecule-1 ectodomain (sICAM-1) as an inhibitor of lymphocyte function-associated molecule-1 interaction with ICAM-1.
Authors: Meyer D M , Dustin M L , Carron C P 
Published: December 2022

Abstract
Intercellular adhesion molecule-1 (ICAM-1) is a member of the Ig superfamily, contains five Ig-like domains comprising the extracellular portion of the molecule, and interacts with lymphocyte function-associated molecule-1 (LFA-1), a member of the beta 2-integrin family. LFA-1/ICAM-1 interaction is important in a variety of cellular events including Ag-specific T cell activation and leukocyte transendothelial migration. Recently, a soluble circulating form of ICAM-1 has been detected in human serum that appears to result from the proteolytic cleavage of membrane ICAM-1. Native and recombinant soluble forms of ICAM-1 have been reported to inhibit LFA-1/ICAM-mediated adhesion in vitro, and it is conceivable that circulating forms of soluble ICAM-1 are regulators of LFA-1/ICAM-1-mediated cell-cell interaction in vivo. We have investigated the properties of the ICAM-1 ectodomain (sICAM453) as an inhibitor of LFA-1 interaction with ICAM-1 in cell- and molecule-based systems. The results show clearly that recombinant sICAM453 can inhibit LFA-1/ICAM-1 interaction. Soluble ICAM-1 inhibited LFA-1-mediated cell adhesion to immobilized sICAM453 and homotypic T-cell aggregation with IC50 in the 20 to 40 microM range. Definitive evidence that sICAM-1 can inhibit LFA-1 interaction with ICAM-1 was obtained by showing that the sICAM-1 inhibited the interaction between LFA-1 protein micelles and ICAM-1 immobilized on plastic. These results clearly show that sICAM453 can bind to LFA-1 and competitively inhibit ICAM-1/LFA-1-mediated cell-cell interaction, albeit at concentrations much greater than found in plasma. As a consequence, it is unlikely that sICAM-1 would antagonize ICAM-1/LFA-1-mediated cellular events in vivo.
Structural restriction in the heavy chain CDR3 of human rheumatoid factors.
Authors: Børretzen M , Randen I , Natvig J B , Thompson K M 
Published: December 2022

Abstract
We have compared the variable regions of 14 new IgM rheumatoid factors (RFs), produced in healthy human immunized donors (HIDs) with RFs originating from patients with rheumatoid arthritis (RA) and monoclonal Ig RFs (paraproteins or M-components, MC). Two groups with very restricted variable region structures were found. Twelve RFs (3 HID, 3 MC, and 6 RA) encoded by variable heavy (VH) chain germ-line genes with closest homology to DP-10 co-express the Kv325 variable light (VL) chain germ-line gene. These RFs have a remarkable restriction in the length (12-14 amino acids) and structure of the CDRH3. One HID RF has a CDRH3 only two amino acids different from the CDRH3 of a MC RF. Two sets of clonally related RFs, one from an RA patient and one from an HID, have CDRH3s that differ by only three amino acids. Five RFs (3 HID, 1 MC, and 1 RA) encoded by VH germ-line gene segments with closest homology to DP-54 all use the Kv328 VL germ-line gene combined to J kappa 1. Four are rearranged to the D21/9 D segment in the same reading frame, with CDRH3s of 16 to 17 amino acids. Three RFs (1 HID, 1 RA, and 1 MC) have CDRH3s differing by only three amino acids. The highly homologous V-regions in RFs from these two groups imply an initial selection to very similar, if not identical, epitopes. However, it remains to be seen whether somatic hypermutation alters the fine specificity of these autoantibodies.
Oral administration of an immunodominant human collagen peptide modulates collagen-induced arthritis.
Authors: Khare S D , Krco C J , Griffiths M M , Luthra H S , David C S 
Published: December 2022

Abstract
Human type II collagen (HuCII) may be one of the autoantigens involved in human rheumatoid arthritis (RA). By using over-lapping peptides, we have previously described an immunodominant region (HuCII.250-270) on HuCII. In the present study, this 21-mer HuCII.250-270 peptide was used as tolerogen, and its effect on both early and effector phase of collagen-induced arthritis (CIA) was examined. Upon immunization with HuCII-derived peptide 250-270, HuCII.250-270-tolerized mice showed diminished T cell proliferation that was mediated by Th1 cytokine, IL-2. More interestingly, oral tolerance with HuCII.250-270 peptide diminishes primarily a Th1 type of immune response. Arthritis severity was reduced markedly in mice orally tolerized with HuCII.250-270 peptide both at early and effector phases. Suppression of CIA at the effector phase by oral administration of HuCII peptide suggests a potential immunotherapeutic use of collagen II peptide in the treatment of human RA.
Growth-related gene product alpha. A chemotactic cytokine for neutrophils in rheumatoid arthritis.
Authors: Koch A E , Kunkel S L , Shah M R , Hosaka S , Halloran M M , Haines G K , Burdick M D , Pope R M , Strieter R M 
Published: December 2022

Abstract
Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product alpha (gro alpha) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro alpha (mean 5.3 +/- 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p &lt; 0.05). RA plasma contained more gro alpha (mean 4.3 +/- 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p &lt; 0.05). RA ST fibroblasts (1.2 x 10(5)/cells/mI RPMI 1640/24 h) produced antigenic gro alpha (mean 0.2 +/- 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-alpha (mean 1.3 +/- 0.3 ng/ml) or IL-1 beta (mean 2.3 +/- 0.6 ng/ml) (p &lt; 0.05). Cells from RA SF also produced gro alpha: neutrophils (PMNs) (10(7) cells/mI/24 h) produced 3.7 +/- 0.7 ng/ml. RA SF mononuclear cells produced gro alpha, particularly upon incubation with LPS or PHA. Immunoreactive ST gro alpha was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p &lt; 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro alpha for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro alpha plays an important role in the ingress of PMNs into the RA joint.
Pathogenicity of T cells responsive to diverse cryptic epitopes of myelin basic protein in the Lewis rat.
Authors: Mor F , Cohen I R 
Published: December 2022

Abstract
The cellular immunology of experimental autoimmune encephalomyelitis, a model for multiple sclerosis, has been studied, for the most part, using T cells directed to dominant epitopes of the Ag myelin basic protein (MBP). To characterize T cells reactive to cryptic epitopes of MBP, we immunized Lewis rats with each of 17 overlapping peptides of the 18.5-kDa isoform of rat MBP. We found that, in addition to the known 71-90 epitope, six other peptides induced active encephalomyelitis in the majority the injected rats. T cell lines raised to six different MBP epitopes were encephalitogenic upon adoptive transfer to naive rats. In contrast to the T cells specific for the dominant 71-90 peptide, the T cell lines reactive to cryptic epitopes were not restricted in their TCR genes to V beta 8.2, and some of the lines caused prolonged disease. Thus, T cells of different specificities and TCR usage can be pathogenic.
Cytotoxic effect of TNF and lymphotoxin on T lymphoblasts.
Authors: Sarin A , Conan-Cibotti M , Henkart P A 
Published: December 2022

Abstract
Recombinant TNF and lymphotoxin trigger the apoptotic death of normal mouse and human T lymphocyte blasts in vitro. This cytotoxic effect does not involve the Fas death pathway and differs from the TNF-triggered death of tumor cells in several respects: 1) It is a slower process, requiring 2 to 3 days; 2) it is blocked, rather than enhanced, by cycloheximide; and 3) based on the agonistic effect of anti-TNF receptor Abs, it involves a synergistic effect of both the 55-kDa TNFR1 and the 75-kDa TNFR2, as opposed to the dominance of TNFR1 for tumor cytotoxicity. The TNF-induced death of blasts is potently inhibited by IL-2, as well as by IL-1, IL-4, IFN-gamma, and IL-12. Because activated T cells secrete both TNF and LT, these findings reveal a new pathway for Ag-induced down-modulation of T cell responses.
Rate of antigen degradation by the ubiquitin-proteasome pathway influences MHC class I presentation.
Authors: Grant E P , Michalek M T , Goldberg A L , Rock K L 
Published: December 2022

Abstract
The effect on MHC class I Ag presentation of enhancing a protein's rate of degradation by the ubiquitin-proteasome pathway was investigated. In extracts of mouse B-lymphoblasts and reticulocytes, as in rabbit reticulocytes, proteins with acidic or basic N-termini are conjugated to ubiquitin and degraded by the 26S proteasome very rapidly. We found that the rate of MHC class I presentation of microinjected beta-galactosidase was enhanced when this antigenic protein was modified with such a destabilizing amino-terminal residue. This enhanced presentation was inhibited by blocking potential ubiquitination sites on the protein through methylation of amino groups and by peptide aldehyde inhibitors of the proteasome. Furthermore, in B lymphoblast cell extracts, the rapid degradation of these beta-galactosidase constructs required ATP and ubiquitin and was blocked by inhibitors of proteasomes. Their rates of degradation in extracts correlated with their rates of class I Ag presentation in vivo. These results indicate that ubiquitin conjugation is a key rate-limiting step in Ag presentation and provide further evidence for a critical role of ubiquitin and the 26S proteasome in generating MHC class I-presented peptides.