bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rat mast cell lines bind to the vascular cell adhesion molecule-1 (VCAM-1) and the mucosal addressin cell adhesion molecule-1 (MAdCAM-1).
Authors: Palecanda A , Briskin M J , Issekutz T B 
Published: December 2022

Abstract
Mast cells are key mediators of allergy and inflammation. Increased mast cell numbers are observed in the gut during helminth infestation and at many sites of inflammation. To determine whether mast cells express functional receptors for endothelial cell adhesion molecules, we studied the adhesion of two rat mucosal-type mast cell lines RBL-1 and RCMC-1 to transfected mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and VCAM-1. Both mast cell lines expressed high levels of alpha4 integrins on their surface and bound to CHO cells transfected with VCAM-1. Anti-alpha4 mAbs, TA-2 and L25, inhibited the specific adhesion of the mast cells to VCAM-1 by about 92 and 63%, respectively. Both of the mast cell lines also demonstrated an increased adhesion to CHO cells transfected with MAdCAM-1. The adhesion of RBL-1 to MAdCAM-1 was also significantly inhibited by the anti-alpha4 mAbs TA-2, L25, and HP2/1 by 39, 76, and 42%, respectively. In addition, RBL-1 cells adhered to both VCAM-1 and MAdCAM-1 under both static and nonstatic (shear) conditions, and this was also inhibited by the anti-alpha4 mAb TA-2. Thus, mucosal-type mast cell lines express functional alpha4 integrins that can mediate adhesion to VCAM-1 and MAdCAM-1. These results suggest a mechanism for mast cell accumulation at sites of inflammation and in the gut.
Bacterial lipopolysaccharide stimulates the production of cytokines and the expression of costimulatory molecules by human peripheral blood dendritic cells: evidence for a soluble CD14-dependent pathway.
Authors: Verhasselt V , Buelens C , Willems F , De Groote D , Haeffner-Cavaillon N , Goldman M 
Published: December 2022

Abstract
To investigate the responses of dendritic cells (DC) during Gram-negative infections, we analyzed the effects of graded doses of LPS on the cytokine profile, phenotype, and allostimulatory potential of human DC generated by culturing plastic-adherent PBMC in presence of IL-4 and granulocyte-macrophage-CSF. First, we found that LPS stimulates the production of high levels of TNF-alpha, IL-6, IL-8, IL-12 by DC and up-regulates their expression of HLA-DR, B7-1, B7-2, and CD40. The effects of LPS were dose dependent, with a significant stimulatory effect already observed at a concentration of 0.1 ng/ml and a plateau being reached at 10 ng/ml. These phenotypic changes correlated with increased allostimulatory properties of LPS-activated DC because DC treated with LPS were significantly more efficient than untreated DC in eliciting IL-2 and IFN-gamma synthesis by alloreactive T cells and stimulating their proliferation. Experiments using neutralizing anti-IL-12 mAb indicated that LPS-induced IL-12 is responsible for the increased production of IFN-gamma but not for the increased proliferation during MLR. Finally, we observed that the DC responses to low levels of LPS (1 ng/ml) were dramatically inhibited by a blocking anti-CD14 mAb, although DC do not express CD14 molecules on their membrane. Experiments using serum depleted of soluble CD14 (sCD14) and sCD14 either purified from human serum or in recombinant form further established that DC respond to LPS via a soluble CD14-dependent pathway.
Adenosine A2a receptor activation delays apoptosis in human neutrophils.
Authors: Walker B A , Rocchini C , Boone R H , Ip S , Jacobson M A 
Published: December 2022

Abstract
Adenosine has both pro- and anti-inflammatory effects on neutrophils. Exposure of cultured neutrophils to 2-chloroadenosine or 5'-N-ethylcarboxamidoadenosine (NECA) decreased apoptosis after 16 h, with half-maximal responses for NECA and 2-chloroadenosine of 7.1 +/- 7.7 and 59.0 +/- 32.0 nM, respectively. Adenosine receptor agonists exhibited a rank order of potency for decreasing apoptosis of 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) &gt; NECA &gt; or = 2-chloro-N6-cyclopentyladenosine &gt; 2-chloro-N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide, which is consistent with the affinity order profile established for human A2a receptors. The reduction in apoptosis in cultured neutrophils at 16 h by CGS 21680 was due to a delay in apoptosis. The addition of CGS 21680 (100 nM) increased the half-life for the appearance of apoptosis from 10.9 +/- 3.1 to 21.0 +/- 1.0 h. Addition of the non-xanthine phosphodiesterase inhibitor 4-(3-butoxy-4-methoxybenzyl)-2-imidazalidinone (Ro-20-1724; 1 microM) enhanced the effects of CGS 21680 at all agonist concentrations. PGE1 (10 microM), PGE2 (0.1-10 microM), and dibutyryl cAMP (5-500 microM) all decreased apoptosis in cultured neutrophils. The enhancement of the effect of adenosine by a phosphodiesterase inhibitor and the similar actions of PGE2, PGE1, and dibutyryl cAMP suggest that this decrease in apoptosis may be mediated by a cAMP-dependent pathway.
Inhibition of nitric oxide synthase for treatment of experimental autoimmune encephalomyelitis.
Authors: Brenner T , Brocke S , Szafer F , Sobel R A , Parkinson J F , Perez D H , Steinman L 
Published: December 2022

Abstract
Aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase, prevented the clinical development of experimental autoimmune encephalomyelitis (EAE) with a reduction in inflammation and demyelination. Administration of AG reduced the expression of nitrosotyrosine in inflammatory lesions in the central nervous system. Cytokine expression, determined by semiquantitative PCR, revealed increased expression of IFN-gamma, IL-10, and TGF-beta, which was associated with protection from EAE, and reduced TNF-alpha, associated with the development of EAE. Furthermore, AG blocked the secretion of nitric oxide, TNF-alpha, and PGE2 in astrocyte cultures. AG did not influence the proliferation response of T cells to a pathogenic epitope of myelin basic protein. Down-regulation of nitric oxide by AG has widespread consequences for cytokine production in central nervous system inflammation and prevents EAE.
Distribution of Antibodies in the Serum and Organs of Rabbits
Authors: Freund Jules 
Published: December 2022

Abstract
The question whether antibodies leave the site of injection or remain fixed there is of considerable theoretical and practical interest. Ransom (1), studying the distribution of diphtheria-antitoxin in dogs in von Behring's laboratory, found antitoxin in the lymph of the thoracic duct and in the blood fifteen minutes after subcutaneous injection. Introducing the antitoxin into the blood stream, he found that the relationsip of the antitoxin titer of the blood and of the lymph of the thoracic duct became constant from six to twenty-four hours after injection. Although these titers decreased with time the equilibrium once established remained constant as long as observations were continued, that is, for four weeks. These observations are in harmony with the view that antitoxin injected into the subcutaneous tissue is absorbed and redistributed to the tissues by the blood stream. There is no aspect of Ransom's work which suggests that antibodies remain at the site of injection.
Antigen Presentation by Dendritic Cells Focuses T Cell Responses Against Immunodominant Peptides: Studies in the Hen Egg-White Lysozyme (HEL) Model1
Authors: Gapin Laurent , Bravo de Alba Yolanda , Casrouge Armanda , Cabaniols Jean Pierre , Kourilsky Philippe , Kanellopoulos Jean 
Published: December 2022

AbstractT lymphocyte responses to a protein Ag are restricted to a limited number of determinants and not to all peptides capable of binding to MHC class II molecules. This focusing of the immune response is defined as immunodominance and has been observed with numerous protein Ags. In the H-2d haplotype, hen egg-white lysozyme (HEL)-specific T lymphocytes react with I-Ed-restricted peptides derived from a single immunodominant (ID) region (HEL 103–117). Moreover, we have recently found that another region of HEL (HEL 7–31) binds to I-Ad molecules and is efficiently processed and presented by splenocytes. HEL7-31 is as tolerogenic as the ID region in HEL transgenic mice. The present report demonstrates that the subdominance of the HEL 7–31 region is not due to a defect in the T cell repertoire, since specific TCRs can be found in all BALB/c mice. We show that normal and lymphoma B cells present efficiently HEL regions 103–117 and 7–31, whereas dendritic cells favor the ID region only. These results suggest that dendritic cells play a major role in the focusing of the immune response against a few antigenic determinants, while B lymphocytes may diversify the T cell response by presenting a more heterogeneous set of peptide-MHC complexes.
Flow-Microfluorometric Monitoring of Oligoclonal CD8+ T Cell Responses to an Immunodominant Moloney Leukemia Virus-Encoded Epitope In Vivo
Authors: Brawand Pierre , Biasi Giovanni , Horvath Clotilde , Cerottini Jean-Charles , MacDonald H. Robson 
Published: December 2022

AbstractThe TCR repertoire of CD8+ T cells specific for Moloney murine leukemia virus (M-MuLV)-associated Ags has been investigated in vitro and in vivo. Analysis of a large panel of established CD8+CTL clones specific for M-MuLV indicated an overwhelming bias for Vβ4 in BALB/c mice and for Vβ5.2 in C57BL/6 mice. These Vβ biases were already detectable in mixed lymphocyte:tumor cell cultures established from virus-immune spleen cells. Furthermore, direct ex vivo analysis of PBL from BALB/c or C57BL/6 mice immunized with syngeneic M-MuLV-infected tumor cells revealed a dramatic increase in CD8+ cells expressing Vβ4 or Vβ5.2, respectively. M-MuLV-specific CD8+ cells with an activated (CD62L−) phenotype persisted in blood of immunized mice for at least 2 mo, and exhibited decreased TCR and CD8 levels compared with their naive counterparts. In C57BL/6 mice, most M-MuLV-specific CD8+CTL clones and immune PBL coexpressed Vα3.2 in association with Vβ5.2. Moreover, these Vβ5.2+Vα3.2+ cells were shown to recognize the recently described H-2Db-restricted epitope (CCLCLTVFL) encoded in the leader sequence of the M-MuLV gag polyprotein. Collectively, our data demonstrate a highly restricted TCR repertoire in the CD8+ T cell response to M-MuLV-associated Ags in vivo, and suggest the potential utility of flow-microfluorometric analysis of Vβ and Vα expression in the diagnosis and monitoring of viral infections.
Delivery of Multiple CD8 Cytotoxic T Cell Epitopes by DNA Vaccination
Authors: Thomson Scott A. , Sherritt Martina A. , Medveczky Jill , Elliott Suzanne L. , Moss Denis J. , Fernando Germain J. P. , Brown Lorena E. , Suhrbier Andreas 
Published: December 2022

AbstractDevelopment of CD8 αβ CTL epitope-based vaccines requires an effective strategy capable of co-delivering large numbers of CTL epitopes. Here we describe a DNA plasmid encoding a polyepitope or “polytope” protein, which contained multiple contiguous minimal murine CTL epitopes. Mice vaccinated with this plasmid made MHC-restricted CTL responses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge models. CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-macrophage CSF, and appeared to be induced in the absence of CD4 T cell-mediated help. The ability to deliver large numbers of CTL epitopes using relatively small polytope constructs and DNA vaccination technology should find application in the design of human epitope-based CTL vaccines, in particular in vaccines against EBV, HIV, and certain cancers.
IFN-γ-Inducing Factor/IL-18 Administration Mediates IFN-γ- and IL-12-Independent Antitumor Effects
Authors: Osaki Tadashi , Péron Jean-Marie , Cai Quan , Okamura Haruki , Robbins Paul D. , Kurimoto Masashi , Lotze Michael T. , Tahara Hideaki 
Published: December 2022

AbstractWe evaluated the mechanism of the antitumor effects of mouse rIFN-γ-inducing factor/IL-18 protein on the growth of mouse tumor cell lines in vivo. Mice received IL-18 before or after challenge with CL8-1, a mouse melanoma cell line. Both regimens significantly suppressed tumor growth and reduced the number of mice with growth of tumor from 60% (3/5) to 20% (1/5). Furthermore, IL-18 administered before and after tumor inoculation completely abrogated the establishment of CL8-1 in all animals. IL-18 administration also significantly suppressed the growth of MCA205, a sarcoma cell line, even when treatment was delayed to 7 days following tumor inoculation. Although IL-18/IL-12 combination therapy had the most significant and immediate antitumor effects, many mice so treated succumbed with markedly elevated serum IFN-γ levels. The antitumor effects of IL-18 were abrogated almost completely when NK cells were eliminated using anti-asialo GM1 Ab administration, but only marginally impaired in IFN-γ or IL-12 gene-disrupted mice. Immunohistochemical staining revealed that the number of the CD8+ T cells, but not CD4+ T cells, found at the tumor site was reduced in animals treated with IL-18. These results indicate that IL-18 has potent antitumor effects mediated by CD4+ T cells and NK cells, but in IFN-γ- and IL-12-independent pathways.
Immunodominance Does Not Result from Peptide Competition for MHC Class II Presentation
Authors: Lo-Man Richard , Langeveld Jan P. M. , Martineau Pierre , Hofnung Maurice , Meloen Robert H. , Leclerc Claude 
Published: December 2022

AbstractCompetition for binding to MHC class II molecules between processed peptides derived from a single protein Ag is considered an important parameter leading to the presentation of a limited set of peptides by APCs. We tested the relevance of this competition process in a model Ag, the MalE protein, by deleting T cell epitopes or by introducing a competitor T cell peptide. We identified in DBA/1 (I-Aq) mice six immunodominant T cell determinants in the MalE sequence, 89–95, 116–123, 198–205, 211–219, 274–281, and 335–341. Synthetic peptides carrying these determinants were classified in three groups as weak, intermediate, or strong I-Aq binders in competition experiments with the PreS:T peptide of hepatitis B surface Ag. In vivo, synthetic MalE peptides with weak and intermediate MHC binding capacity were inhibited in their capacity to stimulate proliferative response in the presence of the PreS:T competitor peptide, whereas the strongest MHC binder was not. Strikingly, the insertion of the potent competitor PreS:T peptide into the MalE sequence, as a single copy or as four copies, did not inhibit the proliferative response to the six immunodominant peptides of the recipient protein. Moreover, deletion in the protein sequence disrupting either the weak (198–205) or strong (335–341) MHC binding determinant of MalE did not modify the proliferative response to the remaining T cell determinants as compared with wild-type MalE protein. Altogether, these results show that peptide competition for MHC binding may not represent the most important event in processes leading to immunodominance.
Toxoplasma gondii-Infected Cells Are Resistant to Multiple Inducers of Apoptosis
Authors: Nash Paul B. , Purner Matthew B. , Leon Ronald P. , Clarke Penelope , Duke Richard C. , Curiel Tyler J. 
Published: December 2022

AbstractInfection with certain intracellular pathogens, including viruses and bacteria, may induce host cell apoptosis. On the other hand, infection with some viruses inhibits apoptosis. Complex protozoan parasites, including Toxoplasma gondii and members of Plasmodium, Leishmania, and Microsporidia, are also obligate intracellular pathogens, yet relatively little is known regarding their subversion of host cell functions. We now report that cells infected with T. gondii are resistant to multiple inducers of apoptosis, including Fas-dependent and Fas-independent CTL-mediated cytotoxicity, IL-2 deprivation, gamma irradiation, UV irradiation, and the calcium ionophore beauvericin. Inhibition of such a broad array of apoptosis inducers suggests that a mechanism common to many, or perhaps all, apoptotic pathways is involved. The inhibitory activity requires live intracellular parasite and ongoing protein synthesis. Despite T. gondii-mediated inhibition of DNA fragmentation, infected cells can still be lysed by CTL.
Superantigen-Activated T Cells Redirected by a Bispecific Antibody Inhibit Vesicular Stomatitis Virus Replication In Vitro and In Vivo
Authors: Fernandez-Sesma Ana , Peluso Richard W. , Bai Xu , Schulman Jerome L. , Levy David E. , Moran Thomas M. 
Published: December 2022

AbstractA bispecific Ab (BsAb) that binds the TCR on T cells and the G protein of the vesicular stomatitis virus (VSV) can redirect staphylococcal enterotoxin B (SEB)-activated T cells to kill VSV-infected cells and to inhibit VSV replication in vitro. Inhibition of virus replication in our system is dependent upon the specificity of the Ab for the viral protein. IFN-γ does not play a very important role in this phenomenon, which is mainly mediated by the release of Pfp from CD8+ T cells. We have used a Stat1 knockout mouse model in which VSV infection is lethal. Infusion of staphylococcal enterotoxin-activated B T cells and bispecific Ab significantly slowed virus progression and prolonged the survival of VSV-infected Stat1 knockout mice in vivo.
Phosphatidylinositol 3-Kinase Mediates Chemoattractant-Stimulated, CD11b/CD18-Dependent Cell-Cell Adhesion of Human Neutrophils: Evidence for an ERK-Independent Pathway
Authors: Capodici Constance , Hanft Simon , Feoktistov Marianne , Pillinger Michael H. 
Published: December 2022

AbstractWe examined the role of phosphatidylinositol 3-kinase (PI 3-K) in FMLP-stimulated cell-cell adhesion of human neutrophils. The specific PI 3-K inhibitors wortmannin and LY294002 inhibited neutrophil homotypic aggregation stimulated by chemoattractants such as FMLP (50% inhibitory concentration (IC50) ≈ 11 nM and 13 μM, respectively) but not PMA. Wortmannin also inhibited FMLP-stimulated adhesion of neutrophils to human endothelial cell monolayers, suggesting a common signaling pathway for homotypic and heterotypic adhesion. Neither CD11b/CD18 expression nor expression of an activation-specific epitope of CD11b/CD18 was affected by wortmannin in FMLP-stimulated cells. Moreover, wortmannin also inhibited the aggregation of egranulate neutrophil cytoplasts that lack the capacity for CD11b/CD18 up-regulation. Although wortmannin inhibited neutrophil lysosomal enzyme release, it had no effect on FMLP-stimulated up-regulation of CD35 in intact neutrophils, suggesting discrepant signaling pathways for specific granule degranulation and secretory vesicle release. Aggregation of human neutrophils is associated with activation of the mitogen-activated protein kinases Erk1 and -2, and Erk is activated in response to PI 3-K in some cell types. However, wortmannin inhibited FMLP stimulation of neutrophil Erk only at concentrations (IC50 ≥ 1 μM) inconsistent with an effect on PI 3-K. Our data indicate that PI 3-K mediates neutrophil adhesion by a mechanism independent of CD11b/CD18 up-regulation, suggesting that PI 3-K acts either parallel to, or downstream of, Erk.
The Glycosyl-Inositol-Phosphate and Dimyristoylglycerol Moieties of the Glycosylphosphatidylinositol Anchor of the Trypanosome Variant-Specific Surface Glycoprotein Are Distinct Macrophage-Activating Factors
Authors: Magez Stefan , Stijlemans Benoı̂t , Radwanska Magdalena , Pays Etienne , Ferguson Michael A. J. , De Baetselier Patrick 
Published: December 2022

AbstractThe TNF-α-inducing capacity of different trypanosome components was analyzed in vitro, using as indicator cells a macrophage cell line (2C11/12) or peritoneal exudate cells from LPS-resistant C3H/HeJ mice and LPS-sensitive C3H/HeN mice. The variant-specific surface glycoprotein (VSG) was identified as the major TNF-α-inducing component present in trypanosome-soluble extracts. Both soluble (sVSG) and membrane-bound VSG (mfVSG) were shown to manifest similar TNF-α-inducing capacities, indicating that the dimyristoylglycerol (DMG) compound of the mfVSG anchor was not required for TNF-α triggering. Detailed analysis indicated that the glycosyl-inositol-phosphate (GIP) moiety was responsible for the TNF-α-inducing activity of VSG and that the presence of the GIP-associated galactose side chain was essential for optimal TNF-α production. Furthermore, the results showed that the responsiveness of macrophages toward the TNF-α-inducing activity of VSG was strictly dependent on the activation state of the macrophages, since resident macrophages required IFN-γ preactivation to become responsive. Comparative analysis of the ability of both forms of VSG to activate macrophages revealed that mfVSG but not sVSG stimulates macrophages toward IL-1α secretion and acquisition of LPS responsiveness. The priming activity of mfVSG toward LPS responsiveness was also demonstrated in vivo and may be relevant during trypanosome infections, since Trypanosoma brucei-infected mice became gradually LPS-hypersensitive during the course of infection. Collectively, the VSG of trypanosomes encompasses two distinct macrophage-activating components: while the GIP moiety of sVSG mediates TNF-α induction, the DMG compound of the mfVSG anchor contributes to IL-1α induction and LPS sensitization.
Identification of CCR8 as the Specific Receptor for the Human β-Chemokine I-309: Cloning and Molecular Characterization of Murine CCR8 as the Receptor for TCA-3
Authors: Goya Iñigo , Gutiérrez Julio , Varona Rosa , Kremer Leonor , Zaballos Angel , Márquez Gabriel 
Published: December 2022

AbstractChemokine receptor-like 1 (CKR-L1) was described recently as a putative seven-transmembrane human receptor with many of the structural features of chemokine receptors. To identify the ligand of CKR-L1, we have studied chemokine-induced calcium mobilization in 293 cells transfected with CKR-L1. Of 20 different chemokines tested, only I-309 was able to elicit a significant calcium mobilization. In addition, I-309 induced the transfectants to migrate in vitro. As expected for chemokine receptor-mediated effects, pertussis toxin, but not cholera toxin, inhibited both the calcium flux and migration of the CKR-L1 transfectants in response to I-309. All of these data support the conclusion that I-309 is a functional ligand for CKR-L1. According to the current chemokine receptor nomenclature, we have designated this gene as CCR8. The murine CCR8 (mCCR8) gene was cloned, and its predicted amino acid sequence showed a 71% identity with that of human CCR8. As human CCR8, mCCR8 is expressed in thymus. Both I-309 and its murine homologue TCA-3 were able to induce calcium mobilization in transiently transfected 293-EBNA cells expressing mCCR8. The affinity of the binding of 125I-labeled TCA-3 to mCCR8 was high (Kd ≈ 2 nM); the binding was prevented completely by an excess of cold TCA-3, and only partially competed (40%) by I-309. The identification of I-309 and TCA-3 as the functional ligands for CCR8 receptors will help to unravel the role of these proteins in physiologic and pathologic situations.