bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevation of corticosteroid-binding globulin in obese strain (OS) chickens: possible implications for the disturbed immunoregulation and the development of spontaneous autoimmune thyroiditis.
Authors: Fässler R , Schauenstein K , Krömer G , Schwarz S , Wick G 
Published: December 2022

Abstract
Basal plasma levels of corticosterone and corticosteroid-binding globulin (CBG) have been investigated in Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis (SAT). Corticosterone was determined radioimmunologically, and CBG by using a highly sensitive radioligand saturation assay. OS chickens displayed total corticosterone levels not different from healthy normal White Leghorn (NWL) chickens. CBG, however, was found to be twice as high in OS chickens as compared with their healthy counterparts, irrespective of sex or age. This quantitative difference in the CBG level is not compensated for by either altered affinity or specificity of the molecule. Furthermore, no differences were found in the response of OS and NWL lymphocytes to the suppressive effect of glucocorticoids in vitro. We therefore assume that OS animals are deficient in free, hormonally active corticosterone. An additional indication for such a diminished glucocorticoid tonus was that in vivo treatment of OS chickens with glucocorticoid hormones, thus increasing the free and active hormone fraction, normalizes the T cell hyperreactivity and significantly reduces thyroid infiltration. Possible pathophysiological implications of a diminished glucocorticoid tonus for spontaneous autoimmunity, as well as possible explanations for the beneficial effects of glucocorticoid treatment on the development of SAT, are discussed.
Epitopes, structural domains, and asymmetry of amino acid residues in SS-B/La nuclear protein.
Authors: Chan E K , Francoeur A M , Tan E M 
Published: December 2022

Abstract
SS-B/La is a conserved cellular phosphoprotein of 46 to 48 KD that is the target antigen of autoantibodies in sera of patients with Sjogren's syndrome and systemic lupus erythematosus. SS-B/La is also known to be associated with certain small cellular and viral RNA, including adenovirus VAI and VAII RNA. Two relatively protease-resistant domains (X and Y) were defined in SS-B from HeLa cells by using human autoantibodies as reagents. Domain X, a methionine-containing nonphosphorylated 28 KD polypeptide, was found to be resistant to partial digestion with six different proteases. Similar domains were also found in calf and rabbit SS-B. Domain Y, a 23 KD polypeptide, was detected after limited digestion with S. aureus V8 and trypsin. This domain contained little if any methionine, but all the detectable phosphorylated amino acids. Among 16 anti-SS-B sera tested by immunoblotting, 11 (69%) were reactive with both domains, three (19%) only with domain X, and two (13%) only with domain Y. These results showed that there are at least two distinct antigenic epitopes on the 46 to 48 KD SS-B/La protein, each located on a separate structural domain. The asymmetric distribution of methionine and phosphorylated amino acid residues in SS-B/La show striking similarity to the two reported domains of the adenovirus 72 KD DNA-binding protein, and raises questions concerning functional similarities that await investigation.
The human B cell-associated antigen CD24 is a single chain sialoglycoprotein.
Authors: Pirruccello S J , LeBien T W 
Published: December 2022

Abstract
The CD24 human B cell-associated antigen was originally characterized in this laboratory with the use of monoclonal antibody BA-1 combined with a standard radioimmuneprecipitation technique, and was reported to be a three chain glycoprotein complex of 45, 55, and 65 kilodaltons. We have compared our standard radioimmuneprecipitation technique (BA-1 ascites followed by rabbit anti-mouse IgM-coated protein A-Sepharose) to BA-1 conjugated directly to CNBr-Sepharose (BA-1-Sepharose) and report striking differences in the electrophoretic profile of CD24 immuneprecipitates. The CD24 immuneprecipitate obtained with BA-1-Sepharose showed a single broad band with a relative mobility of 42 kilodaltons. A series of experiments performed with the two immuneprecipitation techniques, reducing or nonreducing electrophoretic conditions, and addition of preformed mock BA-1 immuneprecipitate to BA-1-Sepharose immuneprecipitates convincingly demonstrated that the previously described 55 and 65 kilodalton components were artifacts caused by co-migration of CD24 with IgG and IgM heavy chains, respectively. Because of the consistent association and co-migration of CD24 with IgG heavy chains, we investigated the possibility that CD24 might be related to the 45 kilodalton Fc-gamma receptor expressed on B cells and eosinophils. We found, however, no evidence for such a relationship by cross adsorption analysis with BA-1-Sepharose and IgG-Sepharose.
Source of the arachidonic acid released on stimulation of rat basophilic leukemia cells.
Authors: Garcia-Gil M , Siraganian R P 
Published: December 2022

Abstract
Triggering of rat basophilic leukemia cells for histamine secretion is accompanied by arachidonic acid release. We studied the source of this arachidonic acid released after IgE or calcium ionophore A23187 stimulation. The 48-hr culture of the cells with [14C]arachidonic acid resulted in labeling of the phospholipids to constant specific activity. After IgE stimulation, 8.8% of the cellular [14C]arachidonate was released; this was predominantly from phosphatidylinositol (PI)/phosphatidylserine (PS) (66.3%), less from phosphatidylethanolamine (PE) (25.9%), and minimally from phosphatidylcholine (PC). In contrast, after ionophore stimulation the cells released 16.4% of cellular [14C]arachidonate, most of this was from PE (55.4%) followed by about equal amounts from PS/PI and PC (24% and 20%, respectively). Therefore, the source of the released arachidonic acid depends on the stimulus. In contrast, the results are different when the cells are cultured for only 2 hr with [14C]arachidonic acid. The label in phospholipids was in PC (44%), PE (38%), and PI/PS (20%); the stimulation of the cells with IgE or ionophore resulted in the release of the [14C]arachidonate from PC (81% and 96%, respectively). This suggests the presence of several pools of phospholipids that are labeled at different rates and have variable proximity and/or accessibility to the phospholipase(s) enzyme(s) activated during cell secretion.
Enhancement by monokines of leukotriene generation by human eosinophils and neutrophils stimulated with calcium ionophore A23187.
Authors: Dessein A J , Lee T H , Elsas P , Ravalese J , Silberstein D , David J R , Austen K F , Lewis R A 
Published: December 2022

Abstract
Human blood eosinophils and neutrophils that had been incubated with the supernatants of cultures of lipopolysaccharide (LPS)-stimulated blood mononuclear cells demonstrated respective enhanced abilities to produce immunoreactive leukotriene C4 (LTC4) and immunoreactive leukotriene B4 (LTB4) after activation by the calcium ionophore A23187. Under optimal conditions, the enhancing effect was observed with the eosinophils (n = 21) and the neutrophils (n = 14) from all but one donor of each type of granulocyte. Enhancement was maximum when granulocytes were preincubated with a 1/3 dilution of LPS-stimulated mononuclear cell culture supernatants for 1 to 2.5 min and were then stimulated with 2.5 microM ionophore for 1 to 2 min (neutrophils) or 15 min (eosinophils). Maximal enhancement ranged from 20 to 4500% for LTC4 generation by eosinophils (geometric mean, 87%) and from 30 to 1600% for LTB4 generation by neutrophils (geometric mean, 105%). There was no enhancement of leukotriene biosynthesis when the LPS-stimulated mononuclear cell culture supernatants and ionophore were added simultaneously to the granulocytes. The enhancing activity for LTC4 generation by eosinophils was removed by washing the cells after the addition of the LPS-stimulated mononuclear cell culture supernatants and before the introduction of ionophore. This enhancing activity was produced by Ig-, Leu-1- adherent blood mononuclear cells, which are presumed to be monocytes; supernatants of adherent cells augmented A23187-induced LTC4 generation by eosinophils from 21 to 2300% (geometric mean, 402%) in 11 experiments and LTB4 generation by neutrophils from 7 to 200% (geometric mean, 60%) in 10 experiments. There was an inverse correlation between the percent enhancement and the LTC4 levels produced by stimulated eosinophils in the absence of the monokine(s) (r = -0.79, p less than 0.01), but not between percent enhancement and the LTB4 levels generated by ionophore-activated neutrophils in the control buffer. The activity of the monocyte-derived enhancing material on each type of granulocyte was relatively heat stable. Enhancement of eosinophil production of LTC4 was associated with an acidic group of monocyte-derived molecules having isoelectric points of 4.2 to 4.3, 4.5 to 4.6, and 4.9, and exhibiting marked heterogeneity in size.(ABSTRACT TRUNCATED AT 400 WORDS)
Human endothelial cells inhibit granulocyte aggregation in vitro.
Authors: Zimmerman G A , Klein-Knoeckel D 
Published: December 2022

Abstract
Granulocyte aggregation in response to circulating or locally released inflammatory mediators may cause vascular injury. The factors that regulate the granulocyte aggregation response and prevent its occurrence are not defined. We found that primary monolayers of human endothelial cells (EC) derived from umbilical veins released products that inhibited granulocyte aggregation. When polymorphonuclear leukocytes (PMN) and EC were incubated together, the subsequent aggregation response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) was inhibited by 40 to 60%, depending in part on the duration of incubation and the concentration of the agonist. Suspension of the granulocytes in albumin-containing buffer that had been rocked with EC monolayers had a similar effect, demonstrating that the EC release a soluble product that modulates the aggregation response. The fMLP concentration-response curve was shifted downward and to the right by EC. Incubation of the granulocytes with endothelial monolayers for various times indicated that the inhibition was maximal at 2 to 3 min, and the PMN responsiveness returned to control over the next 15 min. The inhibiting effect was not selectively directed against fMLP, because incubation of PMN with EC or suspending the PMN in supernatants from endothelial monolayers also inhibited aggregation stimulated by platelet-activating factor, leukotriene B4, and C5a desarg. Release of the inhibitory activity by EC was attenuated by indomethacin, suggesting that the activity is in part due to a cyclooxygenase pathway product. Prostacyclin (PGI2), an eicosanoid produced by EC via the cyclooxygenase pathway, inhibited granulocyte aggregation; however, PGI2 was much less potent as an inhibitor of PMN aggregation than of platelet aggregation. Furthermore, the concentration of PGI2 in buffer that had been incubated with EC was not sufficient to account for the magnitude of the PMN inhibition. The concentration of prostaglandin E2 (PGE2) was also insufficient to completely account for the inhibition. EC that had been treated with indomethacin or aspirin, which blocked the release of PGI2 and PGE2, retained the partial ability to release an activity that blunted granulocyte aggregation; this inhibiting activity was stable at 37 degrees C for 60 min. The results indicate that human EC have the biologic potential to modulate granulocyte aggregation stimulated by inflammatory mediators, and the activity is only partly due to PGI2 and other cyclooxygenase products of arachidonic acid.(ABSTRACT TRUNCATED AT 400 WORDS)
Induction of monocyte-macrophage procoagulant activity by transformed cell lines.
Authors: Rambaldi A , Alessio G , Casali B , Passerini C G , Donati M B , Mantovani A , Semeraro N 
Published: December 2022

Abstract
Human peripheral blood monocytes and mature macrophages were found to produce significant procoagulant activity (PCA), identified as tissue factor, on exposure to a variety of human (K562, HL60, Raji) and murine (TU5, NS-1) transformed cell lines. The monocyte procoagulant response was vigorous, generating PCA to a level nearly comparable to the response to endotoxin, a known stimulant for monocyte PCA. The response was rapid and could be fully elicited, in a dose-dependent fashion, within 4 hr with HL60 and Raji cell lines and within 14 hr with K562, TU5, and NS-1 cells. The monocyte PCA-inducing activity was found to reside in the membrane fraction of transformed cells. Other transformed human (Laz 509, Laz 221, Laz 156, U937, CEM) and murine (L1210, P815, TLX9, WEHI 164) cell lines had little, if any, activity. The induction of monocyte PCA by transformed cells most probably was not due to an allogeneic signal, as 1) the K562 and HL60 cell lines were potent PCA inducers despite the lack of class II histocompatibility antigen expression, whereas Laz 156, which did express HLA antigens, was ineffective; 2) mouse peritoneal macrophages responded with the production of strong PCA to the syngeneic transformed cell lines TU5 and NS-1. The monocyte-macrophage procoagulant response to transformed cell lines appeared to be independent of T lymphocytes. Indeed, monocytes purified on the basis of reactivity with monoclonal antibody Mo2 and sorting or depleted of contaminating T cells by anti-T3 antibody and complement responded similarly to conventional monocyte preparations. The production of tissue factor by monocyte-macrophages in response to exposure to some tumor cells may represent a mechanism whereby blood coagulation is activated in malignancy.
Substance P: binding properties and studies on cellular responses in guinea pig macrophages.
Authors: Hartung H P , Wolters K , Toyka K V 
Published: December 2022

Abstract
The neuropeptide Substance P (SP) has been recognized to modulate functional activities of inflammatory cells. We have previously shown that it mediates macrophage activation. In this study we examined binding characteristics of SP and searched for additional evidence of heightened metabolic activity of guinea pig peritoneal macrophages upon challenge with this peptide. Radioligand studies indicated the existence of a homogeneous class of specific binding sites with high affinity for SP on macrophages. Scatchard analysis yielded an apparent KD of 1.9 +/- 0.4 X 10(-8) M (range: 1.4 to 2.4 X 10(-8) M), which was confirmed by kinetic studies. Binding was dose related, saturable, reversible, and could be inhibited by the SP antagonist (D-Pro2,D-Phe7,D-Trp9)-SP. Examination of peptide structural requirements revealed that both the COOH- and NH2-terminus contribute to receptor-ligand interaction. Other members of the tachykinin group of peptides were devoid of stimulatory action on macrophages. Cellular responses after engagement of the receptor sites by SP included downregulation of the membrane-associated enzyme 5'-nucleotidase and stimulation of synthesis and release of arachidonic acid metabolites, as well as of the lysosomal enzyme ADGase. These actions were specific as evidenced by immunoabsorption experiments. Our findings demonstrate that macrophage activation afforded by SP is effected through a receptor-mediated mechanism. Liberation of proinflammatory and immunomodulating substances in response to SP may be relevant to the pathogenesis of neuroinflammatory disease.
Induction of protective immunity against Schistosoma mansoni by a nonliving vaccine. II. Response of mouse strains with selective immune defects.
Authors: James S L , DeBlois L A 
Published: December 2022

Abstract
The efficacy of a new vaccination procedure against Schistosoma mansoni, involving intradermal injection of nonliving antigen combined with the bacterial adjuvant Mycobacterium bovis strain bacillus Calmette Guérin, was tested in several strains of mice. Development of protection against subsequent infection was compared with in vivo skin test reactivity and in vitro humoral reactivity to soluble and surface-associated schistosome antigens. Significant levels of resistance and immune response were displayed by many inbred mouse strains, including C57BL/6J, C3H/HeN, and CBA/J, as well as outbred Swiss-Webster mice. However, no definite correlation was observed between the level of any particular immune response and the level of resistance to challenge S. mansoni infection. Development of protective immunity was also examined in mice with various immune defects, to determine whether these responses are relevant to resistance in this model. Animals with defective specific immediate hypersensitivity response due to deficiencies in IgE (SJL/J) or mast cell (W/Wv) production displayed strong resistance as a result of immunization. Likewise, mice bearing the lpsd (C3H/HeJ) or xid (CBA/N) mutations, affecting cellular or humoral response to certain thymus-independent antigens, developed significant levels of resistance after immunization. A/J mice, with defects in cellular recognition of bacterial endotoxin as well as deficiencies in natural killer cell activity and complement function, also showed significant protective immunity. Thus, these reactivities do not appear to be essential to the resistance against S. mansoni induced by the nonliving vaccine. Two nonresponder strains were identified, P and BALB/c. P mice were defective in specific delayed hypersensitivity response as well as resistance to infection. However, BALB/c mice showed no obvious immune deficiencies at the time of challenge. These results agreed with previous findings in mice immunized by exposure to radiation-attenuated cercariae with one exception; BALB/c mice were protected by vaccination with irradiated cercariae but not by the nonliving vaccine. Thus, further examination of immune response in mice identified in this study as high and low responder strains should allow characterization of critical immune resistance mechanisms induced by the nonliving vaccine, as well as immune mechanisms operating in common between these two models of resistance to S. mansoni.
The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: direct correlation between reduction of established metastases and cytolytic activity of lymphokine-activated killer cells.
Authors: Mulé J J , Yang J , Shu S , Rosenberg S A 
Published: December 2022

Abstract
Our previous studies demonstrated that the incubation of human peripheral blood lymphocytes or murine splenocytes in recombinant interleukin 2 (RIL 2) resulted in the generation of lymphokine-activated killer (LAK) cells capable of lysing a broad spectrum of fresh tumors in short-term chromium-release assays. Moreover, injections of LAK cells plus RIL 2 were highly effective in eliminating established 3 day metastases in the lung and liver (1-3). We have examined several parameters to define whether or not the cytolytic activity of LAK cells as measured in vitro correlated directly with the in vivo anti-tumor efficacy of adoptively transferred LAK cells. LAK cells plus RIL 2 could mediate marked reductions of established pulmonary metastases in mice rendered T cell deficient by adult thymectomy and lethal, total body irradiation followed by reconstitution with T cell-depleted bone marrow and spleen cells. Thus there was no requirement for additional T lymphocytes of host origin for successful therapy with adoptively transferred LAK cells plus RIL 2. Fresh splenocytes depleted of T cells by anti-Thy-1.2 monoclonal antibody plus complement generated LAK cells that were as highly lytic to fresh tumor in vitro and were as effective in reducing established pulmonary metastases as those generated from untreated or complement-treated splenocytes. Thus the precursor to LAK cells with anti-tumor activity in vitro and in vivo did not express the Thy-1 antigenic marker. In contrast, treatment of LAK effector cells (those generated from a 3-day incubation of fresh, normal splenocytes in RIL 2) with anti-Thy-1.2 antibody plus complement reduced or abolished their in vitro cytolytic activity. However, when combined with the systemic administration of RIL 2, these T cell-depleted, non-lytic LAK cells remained as effective in reducing the number of established pulmonary metastases upon adoptive transfer as untreated or complement-treated lytic LAK cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness.
Authors: Rook A H , Kehrl J H , Wakefield L M , Roberts A B , Sporn M B , Burlington D B , Lane H C , Fauci A S 
Published: December 2022

Abstract
Type beta transforming growth factor (TGF-beta) is a unique polypeptide that has been isolated from a number of different tissues and can induce the phenotypic transformation of non-neoplastic fibroblasts as measured by the stimulation of their growth in soft agar. Recently, TGF-beta has been demonstrated to exert profound inhibitory effects on T and B lymphocyte proliferation. In this study, the effects of TGF-beta on natural killer (NK) cell function were investigated. After 20 hr of culture in the presence of TGF-beta, the NK activity of peripheral blood lymphocytes (PBL) was significantly reduced compared with PBL cultured in medium alone. Similarly, TGF-beta produced a significant depression in the cytolytic activity of highly enriched large granular lymphocytes (LGL). This effect of TGF-beta appeared to be mediated directly on the effector cells, because cultivation of the K562 target cells in TGF-beta did not affect target cell susceptibility to lysis. Binding studies with 125I-TGF-beta indicated that LGL possess approximately 1400 high-affinity (Kd = 1PM) receptors/cell, which represents a considerably higher affinity receptor for TGF-beta than that found on fibroblasts. Culturing of PBL and LGL in TGF-beta resulted in a marked blunting of the boosting of NK cytolysis by interferon-alpha but not by interleukin 2, which suggested that TGF-beta may down-regulate interferon-alpha receptors on NK cells. These results, indicate that in addition to inhibitory effects on T and B cells, TGF-beta also inhibits NK cell function. Although the in vivo role of TGF-beta is presently undefined, it may be an important immunoregulatory protein that has a negative influence on lymphocyte activation.
5C6-F4, a novel 100,000-dalton rat lymphocyte activation antigen defined by monoclonal antibody.
Authors: Uede T , Kohda H , Yuasa H , Osawa H , Diamantstein T , Yodoi J , Ishii Y , Kikuchi K 
Published: December 2022

Abstract
Con A-activated rat thymocytes were used to immunize mice, and immune spleen cells were fused with NS/1 myeloma cells. One clone, designated 5C6-F4, reacted strongly with Con A-activated rat thymocytes and some LPS-activated rat spleen cells but not with normal thymocytes, spleen cells, or bone marrow cells of rat origin. The 5C6-F4 did not react with Con A-activated thymocytes of mouse origin. Immunoprecipitation of 5C6-F4 antigen from surface-iodinated Con A-activated rat thymocytes or LPS-activated rat spleen cells revealed its m.w. to be approximately 100,000. The kinetic studies of the expression of 5C6-F4 antigen revealed that 5C6-F4 antigen was detectable at 6 hr after Con A stimulation of rat spleen cells, whereas IL 2 receptor (IL 2R) was detectable at 12 hr. The appearance of 5C6-F4 antigen and IL 2R precede the onset of DNA synthesis of Con A-activated spleen cells. Thus, 5C6-F4 antigen is classified as early activation antigen. The 5C6-F4 inhibits the lymphocyte proliferation induced by mitogen and the IL 2-driven rat T cell proliferation. Sequential immunoprecipitation study as well as binding inhibition study indicated that the 5C6-F4 antigen is distinct from IL 2R molecule. The 5C6-F4 antigen appears to be a novel rat lymphocyte activation antigen that exhibits immunoregulatory function and also may serve as a useful marker of T cell activation.