bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hodgkin's cell lectin, a lymphocyte adhesion molecule and mitogen.
Authors: Paietta E , Stockert R J , McManus M , Thompson D , Schmidt S , Wiernik P H 
Published: December 2022

Abstract
We have previously shown a novel galactose/N-acetylgalactosamine specific lectin activity (Hodgkin's disease (HD) lectin) on the surface of cultured HD cells (lines L428, its variants, and line L540) to mediate lymphocyte adhesion. We here demonstrate that both surface membrane-bound and secreted HD lectin activities participate in the activation of agglutinated lymphocytes. Among known adhesion molecules expressed by the HD cells, only the intercellular adhesion molecule-1 (ICAM-1) contributed to this activation as an alternative PBL binding site. As yet we have not identified the cellular ligand(s) for the HD lectin on the lymphocyte surface. Pretreatment of lymphocytes with mAb to the accessory molecules CD2, CD3, CD4, CD8, CD11b, or CD11c did not interfere with their response to HD cells. mAb to CD11a (LFA-1), the alleged ligand of ICAM-1, inhibited the ICAM-1 but not the HD lectin-mediated lymphocyte stimulation. Although lymphocyte binding could proceed via either pathway, lymphocyte activation always depended upon factors secreted by the HD cells, one of which we identified as a soluble form of the HD lectin based on its shared properties with the membrane-bound form including immunologic cross-recognition and carbohydrate-binding specificity. Although HD cell-conditioned medium alone stimulated lymphocytes, HD cell plasma membranes could compensate for low concentrations of this medium. In addition, resting lymphocytes, normally unresponsive, were triggered into DNA synthesis by growth medium when cocultured with HD cell membranes. The unique functions of the surface-expressed HD lectin and its soluble counterpart as lymphocyte adhesion molecule and mitogen might be physiologically relevant to the severe immunodeficiencies occurring in patients with HD.
Specificity of peptide binding by the HLA-A2.1 molecule.
Authors: Shimojo N , Maloy W L , Anderson R W , Biddison W E , Coligan J E 
Published: December 2022

Abstract
The HLA-A2 molecule contains a putative peptide binding site that is bounded by two alpha-helices and a beta-pleated sheet floor. Previous studies have demonstrated that the influenza virus matrix peptide M1 55-73 can sensitize target cells for lysis by HLA-A2.1-restricted virus-immune CTL and can induce CTL that can lyse virus-infected target cells. To assess the specificity of peptide binding by the HLA-A2.1 molecule, we examined the ability of seven variant M1 peptides to be recognized by a panel of M1 55-73 peptide-specific HLA-A2.1-restricted CTL lines. The results demonstrate that five out of the seven variant M1 55-73 peptides could be recognized by A2.1-restricted M1 55-73 peptide-specific CTL lines. The two variant peptides that were not recognized by any CTL could bind to HLA-A2.1 as indicated by their ability to compete for presentation of the M1 55-73 peptide. In addition, 5 of a panel of 24 unrelated peptides tested could also compete for M1 55-73 presentation by HLA-A2.1. One peptide derived from the sequence of a rotavirus protein could sensitize HLA-A2.1+ targets for lysis by M1 55-73 peptide-specific CTL. We conclude from these studies that: 1) the HLA-A2.1 molecule can bind a broad spectrum of peptides; 2) T cells selected for the ability to recognize one peptide plus a class I molecule can actually recognize an unrelated peptide presented by that same class I molecule; and 3) a stretch of three adjacent hydrophobic amino acids may be an important common feature of peptides that can bind to HLA-A2.1.
Synergistic effects of phorbol ester and INF-gamma on the induction of indoleamine 2,3-dioxygenase in THP-1 monocytic leukemia cells.
Authors: Edelstein M P , Ozaki Y , Duch D S 
Published: December 2022

Abstract
Indoleamine 2,3-dioxygenase (IDO) is a flavin-dependent enzyme which uses superoxide anion as a cosubstrate to catalyze the decyclization of the pyrrole ring of L-tryptophan to form formylkynurenine. This enzyme is induced in some tumor cells after treatment with IFN-gamma. The mechanism of induction of IDO in tumor cells by IFN-gamma was studied in THP-1 human monocytic leukemia cells. Before the addition of IFN-gamma, no IDO could be detected in these cells. Treatment of THP-1 cells with IFN-gamma produced an induction of IDO, with peak activity occurring 72 to 96 h after addition of IFN-gamma. Because phorbol esters are known to induce many enzymes in cells, most likely through the activation of protein kinase C, the effects of PMA on the induction of IDO were determined. PMA potentiated the IFN-gamma-induced elevation of IDO, but by itself, was unable to induce enzyme activity. Maximum induction of IDO in the presence of PMA and IFN-gamma was obtained by preexposure of the cells to PMA for 48 h before the addition of IFN-gamma. Maximum induction of IDO after the addition of IFN-gamma occurred 24 to 48 h after addition of the cytokine to the culture medium. However, the induction of IDO does not appear to be potentiated through the activation of protein kinase C, because the addition of the protein kinase C inhibitor H-7 had no effect on the induction of IDO when the cells were exposed to PMA and IFN-gamma. Moreover, diacylglycerol was unable to replace PMA in these studies. Studies with cAMP and cGMP analogs suggest a role for these compounds in the regulation of IDO expression.
Anaphylactoid reactions mediated by autoantibodies to cholesterol in miniature pigs.
Authors: Wassef N M , Johnson S H , Graeber G M , Swartz G M , Schultz C L , Hailey J R , Johnson A J , Taylor D G , Ridgway R L , Alving C R 
Published: December 2022

Abstract
Antoantibodies to cholesterol were detected and purified from normal (nonimmunized) pig serum. The antibodies were assayed by ELISA with crystalline cholesterol as an Ag and by C-dependent damage to cholesterol-laden liposomes. Intravenous injection of liposomes containing cholesterol into anesthetized animals caused decreased hemolytic complement titers, and induced a reaction consisting of transient neutropenia, thrombocytopenia, respiratory distress, cyanosis, pulmonary and systemic hypertension, and decreased cardiac output. Plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha increased 1300 and 200%, respectively, and leukocyte and platelet counts decreased by 36 and 38%, respectively. Injection of cholesterol-free liposomes did not induce the reaction. These results show that naturally occurring autoantibodies to cholesterol can initiate C activation and can be associated with anaphylactoid reaction to exogenously administered cholesterol in pigs.
Nonionic block polymer surfactants enhance the avidity of antibodies in polyclonal antisera against Streptococcus pneumoniae type 3 in normal and Xid mice.
Authors: Van Dam G J , Verheul A F , Zigterman G J , De Reuver M J , Snippe H 
Published: December 2022

Abstract
Avidities of antibody (sub)classes in polyclonal antisera against Streptococcus pneumoniae type 3 (S3) can be (semi) quantitatively determined with a specific inhibition ELISA. A hexasaccharide was isolated from the hydrolyzed S3 capsular polysaccharide and coupled to a protein-carrier. Mixtures containing these conjugates and nonionic block polymer (NBP) surfactants were used for immunization. After various immunizations of these conjugates without NBP the anti-S3 specific antibodies of IgM and IgG2a isotype decreased in both antibody level and avidity. The adjuvants NBP 1501 and L121 not only enhanced the hexasaccharide-protein induced IgM and IgG antibody levels but also clearly increased the avidity of the two antibody (sub)classes IgM and IgG2a. This effect was observed in normal (data not shown) and X-linked immunodefective mice. A maturation of the IgG antibody response was realized by the second immunization with hexasaccharide-protein conjugate whereas the third immunization showed no further increase in antibody level and avidity.
Molecular cloning of rat cytolysin.
Authors: Ishikawa H , Shinkai Y , Yagita H , Yue C C , Henkart P A , Sawada S , Young H A , Reynolds C W , Okumura K 
Published: December 2022

Abstract
Rat cytolysin is one of the cytolytic factors present in the cytoplasmic granules of rat NK-like cytolytic cells and purified cytolysin exhibits an apparent Mr or 70 kDa. Cytolysis produced by cytolysin occurs in the presence of Ca2+ and is accompanied by the formation of membrane lesions of 160 A diameter. We have isolated a cDNA encoding rat cytolysin from the cDNA library of a rat large granular lymphocyte (LGL) cell line, by hybridization of the rat library with a cDNA probe for mouse perforin. The amino acid sequence deduced from the nucleotide sequence of the isolated cDNA insert indicates that the mature cytolysin protein consist of 534 amino acids with a leader peptide of 20 amino acids. The protein contains two functionally important domains: the first domain is believed to contain the transmembrane channel and the second domain consists of an epidermal growth factor-type "class B" cysteine-rich region. A comparison with mouse perforin indicates that the two genes are very similar (89.9% nucleotide and 84.9% amino acid identity). Northern blot hybridization analysis indicates that cytolysin mRNA is expressed in rat lymphocytes (lymphokine-activated killer cells and LGL cells) and LGL cell lines.
Identification and characterization of a cell-surface molecule that is selectively induced on rat lymphokine-activated killer cells.
Authors: Imboden J B , Eriksson E C , McCutcheon M , Reynolds C W , Seaman W E 
Published: December 2022

Abstract
We have identified a 40- to 45-kDa cell-surface molecule designated gp42, that is expressed in high levels by rat lymphokine-activated killer (LAK) cells of NK cell origin. gp42 cannot be detected on the precursors of LAK cells and is not present on resting or activated T cells. Rather, expression of gp42 is selectively induced on NK cells by the high concentrations of rIL-2 that are required for the induction of LAK activity. Although the function of gp42 is not known, the selective nature of its expression suggests a role for this molecule in regulating responses that are unique to IL-2-activated NK cells.
The age-dependent loss of bone marrow B cell precursors in autoimmune NZ mice results from decreased mitotic activity, but not from inherent stromal cell defects.
Authors: Kruger M G , Riley R L 
Published: December 2022

Abstract
The formation of B lymphocytes is abnormal in autoimmune NZB and (NZB x NZW)F1 mice. With age, the proportion of sIg- Ly-5(220)+ pre-B cells and less mature B cell progenitors in the bone marrow progressively declines, reaching only approximately one-third of normal levels in 20-wk-old NZ mice. To determine the mechanisms responsible for the deficiency of NZ B lineage precursors, the mitotic activity of sIg- Ly-5(220)+ bone marrow cells in vivo was determined in NZ and conventional inbred mice as a function of age. The proportion of sIg- Ly-5(220)+ B cell precursors in (S + G2/M) stages of the cell cycle steadily decreased with age in NZ autoimmune mice. Furthermore, upon metaphase arrest, the rate of entry of sIg- Ly-5(220)+ bone marrow cells into G2/M also decreased with age in NZ mice. Therefore, the mitotic activity of sIg- Ly-5(220)+ B cell precursors is substantially decreased in NZ mice greater than or equal to 20 wk of age. The capacity of the bone marrow stromal microenvironment of NZ mice to support B lineage precursor growth was tested in two ways: 1) the capacity of preformed NZ bone marrow stroma to support B lineage cell growth in long term bone marrow cell culture under lymphopoietic conditions was assessed and 2) the capacity of NZ bone marrow B lineage precursors to expand in vivo after sublethal (200 rad) whole body irradiation was determined. Stroma derived from adult NZ mice supported the growth and development of B lineage lymphocytes in long term bone marrow cell culture to a greater extent than did age-matched conventional murine stroma. Furthermore, sublethal irradiation of older adult NZ mice resulted in some expansion of bone marrow sIg- Ly-5(220)+ B cell precursors in vivo. Therefore, the deficiency of B cell progenitors in the bone marrow of older NZ autoimmune mice is associated with diminished mitotic activity. However, this does not result from defects in the capacity of NZ bone marrow stroma to permit B lineage cell expansion as determined by both in vitro and in vivo experiments. In the absence of a detectable stromal cell defect, it is possible that an active inhibitory process within the bone marrow influences the mitotic activity of B cell precursors in NZ mice.
Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor.
Authors: Selmaj K W , Farooq M , Norton W T , Raine C S , Brosnan C F 
Published: December 2022

Abstract
The effect of cytokines on astrocytes cultured from mature bovine brain was determined both in a serum-containing medium and in a chemically-defined medium. The results showed that in serum-free medium, human TNF and, to a lesser degree, IL-6 and lymphotoxin, were mitogenic for astrocytes. Increased uptake of [3H]thymidine could be detected within 36 h in vitro and its presence in astrocytes was confirmed by autoradiography. In contrast, neither IL-1 alpha nor IL-1 beta induced astrocyte proliferation in serum-free medium but showed some synergistic effect with serum after 72 h. The proliferative effect of TNF and IL-6 was confirmed by cell counting. None of the cytokines tested was toxic for astrocytes as measured by 51Cr release. No mitogenic effect for oligodendroglia, purified from the same source, was detected. The results support a role for products of activated inflammatory cells in the development of astrocyte proliferation that may contribute to the reactive gliosis found in white matter diseases of the central nervous system such as multiple sclerosis.
IL-1 secretion by macrophages. Enhancement of IL-1 secretion and processing by calcium ionophores.
Authors: Suttles J , Giri J G , Mizel S B 
Published: December 2022

Abstract
In the present study we have demonstrated that the murine IL-1 alpha precursor lacks a cleavable signal sequence and does not undergo cotranslational translocation across microsomal membranes in vitro. Culture supernatants of the murine macrophage cell line, P388D, or from normal peritoneal macrophages collected within 0.5 to 3 h after stimulation contained the 33,000 m.w. precursor as the predominant form of IL-1 alpha. Over an 18-h period, the level of low m.w. IL-1 alpha increased as the secreted precursor was processed by extracellular and/or cell surface-associated proteolytic enzymes. The calcium ionophores A23187 and ionomycin were found to dramatically enhance the release and processing of murine and human IL-1. The rapid release of IL-1 in response to a change in the intracellular level of calcium does not appear to be caused by release of a membrane-bound form of the protein, nor is there evidence that IL-1 is packaged and released from cytoskeletal associated secretory granules. In marked contrast, calcium ionophores do not induce secretion of IL-1 from a nonmacrophage cell line that synthesizes but does not normally secrete IL-1. Our results suggest that activated macrophages possess a novel processing independent, possibly calcium-dependent, mechanism that allows for the release of the precursor forms of IL-1 alpha and IL-1 beta.
Constitutive and induced phosphorylation of the alpha- and beta-chains of the CD11/CD18 leukocyte integrin family. Relationship to adhesion-dependent functions.
Authors: Buyon J P , Slade S G , Reibman J , Abramson S B , Philips M R , Weissmann G , Winchester R 
Published: December 2022

Abstract
We sought to determine whether the activation event which renders the CD11/CD18 leukocyte integrin/Leu-CAM glycoproteins capable of promoting cell to cell adhesion was associated with the induced posttranslational modification of phosphorylation. In neutrophils, two species of alpha-chains, a predominant CD11b 165-kDa subunit and a minor 150-kDa CD11c subunit were found to be constitutively phosphorylated. However, the 95-kDa CD18 common beta-chain was not phosphorylated in resting cells but became strongly phosphorylated in cells incubated with PMA. The beta-chain was phosphorylated in a dose-related manner within 1 min of the addition of PMA, reached maximal intensity between 4 to 10 min, and remained fully phosphorylated at 30 min. The similarities of the kinetics of homotypic aggregation induced by PMA to the time course of phosphorylation suggest that phosporylation may be relevant to at least this type of Leu-CAM-dependent adhesion. In contrast, in the presence of FMLP which induces aggregation with different kinetics than PMA, no phosphorylation of the common beta-chain was observed over a time interval of from 30 s to 10 min further emphasizing the apparent differences in the two modes of activation to an adhesive state. The phosphorylated species on neutrophils were readily detected by immunoprecipitation with each CD18 mAb and most but not all CD11b mAb which otherwise precipitated 125I-labeled CD11b species suggesting that the CD11b alpha-chain labelled with 32P may differ slightly from the 125I-labeled species in terms of its recognition by certain CD11b mAb. In mononuclear cells, similar constitutive phosphorylation of the CD11a and CD11c alpha-chains was observed that remained unchanged in the presence of either FMLP or PMA. As was demonstrated in neutrophils, phosphorylation of the CD18 beta-chains of mononuclear cells was not constitutive but was induced in the presence of PMA and not FMLP. Taken together these data suggest the existence of specific recognition sites on beta-chains for a regulatory kinase-phosphatase system.
Immunogenicity of recombinant IL-2 modified by covalent attachment of polyethylene glycol.
Authors: Katre N V 
Published: December 2022

Abstract
Human rIL-2, expressed and purified from Escherichia coli, is currently being tested as an anticancer therapeutic agent. Some of the patients undergoing clinical trials with rIL-2 have developed antibodies to rIL-2. We describe a chemical modification of rIL-2 that reduces its immunogenicity. rIL-2 has been chemically modified with a water soluble polymer, monomethoxy polyethylene glycol (PEG). This covalent conjugate PEG-rIL-2 has enhanced solubility and extended in vivo circulation. Attachment of PEG to rIL-2 reduces its immunogenicity when tested in rabbits and in mice. Ag-specific IgG antibody titers were 100 to 1000-fold lower when PEG-rIL-2 was used as the Ag, compared to rIL-2. In a long term study, 7 of 10 rabbits injected with PEG-rIL-2 had no Ag-specific IgG antibody response. In these seven rabbits, the in vivo behavior of the injected PEG-rIL-2 remained essentially unchanged after repeated immunizations. PEG-rIL-2 injected before rIL-2 injections, immunosuppressed the antibody response to rIL-2 in rabbits. The maintenance of the systemic exposure of PEG-rIL-2 after repetitive dosing is related to its decreased immunogenicity. Thus, the PEGylation (covalent attachment of PEG) of rIL-2-enhances its potential as an anticancer therapeutic.
Recombinant, truncated CD4 molecule (rT4) binds IgG.
Authors: Lederman S , Yellin M J , Cleary A M , Gulick R , Chess L 
Published: December 2022

Abstract
CD4 is a cell surface glycoprotein that identifies the subset of human T lymphocytes that induces sIg+ B lymphocytes to differentiate and secrete Ig after intimate T-B cell contact. In the course of studying a recombinant, truncated form of CD4 (rT4) we noticed that goat antibodies of apparently irrelevant specificities bound to immobilized rT4. To directly study whether rT4 interacts with Ig molecules, purified human IgG was added to rT4-coated wells and a dose-dependent interaction between IgG and rT4 was observed by ELISA. Purified myeloma IgG proteins bound to immobilized rT4 with the same avidity as polyclonal IgG that suggests that rT4-IgG binding was not due to the presence of anti-rT4 antibodies in the IgG fraction. IgG from 6 sera bound to rT4 in concentration dependent manner similar to purified IgG. Immobilized rT4 specifically bound IgG, and not IgM, IgA, IgD, or beta 2-microglobulin. The specific interaction of rT4 and IgG was also observed when IgG or IgM were immobilized, demonstrating that IgG binding was not a unique property of immobilized rT4. As with low affinity receptors for IgG, rT4 bound heat aggregated IgG with increased avidity. Neither anti-CD4 mAb nor dextran sulfate inhibited rT4-IgG binding. rT4 bound Fc but not F(ab)2 fragments. Each of the purified IgG subclasses; IgG1, 2, 3, and 4 bound to rT4 with similar avidity. Taken together, these data suggest that rT4 specifically interacts with a public structure on IgG Fc.
Interactions between murine B lymphocyte surface membrane molecules. Loaded but not free receptors for complement and the Fc portion of IgG co-cap independently with cross-linked surface Ig.
Authors: Tsokos G C , Kinoshita T , Thyphronitis G , Patel A D , Dickler H B , Finkelman F D 
Published: December 2022

Abstract
We have investigated the possible physical interactions between CR, receptors for the Fc gamma R and surface Ig (sIg) on the surface membrane of murine B lymphocytes. We used the rat mAb to murine CR, 8C12, and 7G6, as CR ligands, and soluble Ag-antibody complexes as FcR ligands; and F(ab')2 fragments of rabbit antibodies specific for mouse IgM and IgD as sIg ligands. We have found that: 1) sIg, CR, and Fc gamma R are not directly linked, because capping of any one did not affect the expression of the others; 2) the mAb 8C12 and 7G6 failed by themselves to cross-link CR; 3) soluble Ag-antibody complexes crosslinked some, Fc gamma R on a minority of Fc gamma R+ lymphocytes; 4) once loaded with anti-CR mAb, CR co-capped with sIg when sIg was cross-linked; 5) once loaded with Ag-antibody complexes, Fc gamma R also co-capped with sIg when sIg was sIg was cross-linked; 6) loading of Fc gamma R did not affect the co-capping of surface CR with cross-linked sIg and conversely, loading of CR did not affect the co-capping of Fc gamma R with cross-linked sIg; only loaded CR or Fc gamma R co-capped with sIg regardless of the status of the other surface molecule; 7) neither loaded nor free CR co-capped with cross-linked Fc gamma R, and neither loaded nor free Fc gamma R co-capped with cross-linked CR. These results demonstrate that both Fc gamma R and CR independently become associated with sIg when either receptor is loaded and sIg is cross-linked.
Unmethylation of specific sites in the 5' region is critical for the expression of murine alpha Fc gamma R gene.
Authors: Bonnerot C , Amigorena S , Fridman W H , Even J , Daëron M 
Published: December 2022

Abstract
Three subtypes of murine low-affinity receptors for IgG (Fc gamma RII) have been identified. One is encoded by the alpha Fc gamma R gene, two are encoded by the beta Fc gamma R gene. In the present work, we examined whether DNA methylation might control expression of the alpha Fc gamma R gene. We found that, in DNA from a panel of Fc gamma R(+) and (-) cell lines, two MspI sites of the alpha Fc gamma R gene were selectively unmethylated only in the two cell lines containing alpha transcripts. These sites, separated by a distance of 1.2 kb, are located in the 5' region of the gene. All other MspI sites were methylated in all cell lines. Furthermore, 5-azacytidine induced the demethylation and the expression of the alpha Fc gamma R gene in the Fc gamma R(-) thymoma BW5147. Both alpha Fc gamma R gene transcripts and corresponding protein products became detectable in 5-azacytidine-treated cells. The alpha Fc gamma R gene was also demethylated and expressed in mouse spleen cells cultured with human rIL-2. We conclude that a correlation links the unmethylation and the expression of the alpha Fc gamma R gene in murine cell lines as well as in nontransformed lymphoid cells responding to a physiological stimulus.