bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunologic effects of interferon-alpha in man: treatment with human recombinant interferon-alpha suppresses in vitro immunoglobulin production in patients with chronic type B hepatitis.
Authors: Peters M , Walling D M , Kelly K , Davis G L , Waggoner J G , Hoofnagle J H 
Published: December 2022

Abstract
The effect of human recombinant interferon-alpha on lymphocyte proliferation and differentiation was studied in 18 patients with chronic type B hepatitis who were participating in a randomized controlled trial of interferon-alpha therapy. Peripheral blood mononuclear cells (PBMC) were obtained by lymphopheresis before and during a 4 mo course of interferon. Pokeweed mitogen-induced immunoglobulin synthesis by PBMC obtained from patients before therapy was similar to that of PBMC from normal individuals. However, after 2 wk treatment with human recombinant interferon-alpha mitogen-induced immunoglobulin production was decreased by an average of 50%. Staining for cytoplasmic immunoglobulin revealed decreases that paralleled secreted immunoglobulin, indicating that interferon-alpha treatment inhibited immunoglobulin synthesis. Mixing autologous T and B cell enriched populations from before and during interferon treatment revealed that the decrease in immunoglobulin synthesis involved a defect in the B cell-enriched population. In contrast to immunoglobulin synthesis, pokeweed mitogen-induced lymphocyte proliferation was not significantly affected by in vivo administration of interferon-alpha. Thus a major effect of in vivo interferon-alpha on immunoregulation in patients with chronic type B hepatitis appears to be an inhibition of the late stages of B cell differentiation into immunoglobulin producing and secreting plasma cells.
Down-regulation of interleukin 1 (IL 1) receptor expression by IL 1 and fate of internalized 125I-labeled IL 1 beta in a human large granular lymphocyte cell line.
Authors: Matsushima K , Yodoi J , Tagaya Y , Oppenheim J J 
Published: December 2022

Abstract
The regulation of interleukin 1 (IL 1) receptor expression on a human large granular lymphocyte cell line, YT, and fate of internalized 125I-labeled IL 1 beta (125I-IL 1 beta) were studied. YT cells were selected for this study, because this cell line expresses a large number of specific high-affinity receptor for IL 1, responds biologically to exogenously added IL 1 by expressing high-affinity IL 2 receptors, and does not produce IL 1. YT cells constitutively express approximately 7 X 10(3) IL 1 receptors/cell with a Kd approximately 10(-10) M. Neither IL 2, phorbol myristic acid, nor lipopolysaccharide affected the total binding of 125I-IL 1 beta by YT cells. In contrast, the capacity of YT cells to bind 125I-IL 1 beta when incubated at 37 degrees C for 3 to 16 hr with a low dose of purified IL 1 beta (approximately 6 U/ml) was reduced by greater than 80%. The loss of binding capability gradually recovered by 16 hr after removal of IL 1 beta from cultured YT cells. The apparent loss of IL 1 receptor expression was accompanied by the internalization of 125I-IL 1 beta into cells. Acid treatment of YT cells to remove bound 125I-IL 1 beta at 4 degrees C showed that 50% of the 125I-IL 1 beta bound to cells could no longer be recovered after 30 min at 37 degrees C, and this increased to 80% after 3 hr at 37 degrees C. Fractionation of cell extracts on Percoll gradient additionally showed 125I-IL 1 beta to appear intracellularly after receptor binding on plasma membranes, and to be successively transferred to some membranous organelles (d approximately equal to 1.037) through an intermediate density organelle (d approximately equal to 1.050), and to finally end up in lysosomal cell fractions (d approximately equal to 1.05 to 1.08) after approximately 3 hr at 37 degrees C. Only approximately 5% of internalized 125I-IL 1 beta was released into culture media by 6 hr of incubation at 37 degrees C. However, the radioactivity in the TCA soluble fraction of the culture media increased gradually by 6 hr and a lysosomotropic enzyme, ethylamine, significantly inhibited both the transfer of internalized 125I-IL 1 beta to the lysosomal fraction and the degradation of 125I-IL 1 beta. This study represents the first evidence of autoregulation of IL 1 receptors by IL 1 and internalization of IL 1 molecules after binding to receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
Recombinant IL 2 but not recombinant interferon-gamma stimulates both proliferation and IgM secretion in a Ly-1+ clone of neoplastic murine B cells (BCL1).
Authors: Brooks K H , Vitetta E S 
Published: December 2022

Abstract
We have used a lymphokine-responsive clone (3B3) of B leukemia cells (BCL1) to examine the effects of several recombinant and purified lymphokines. Cells from BCL1-3B3 were induced to secrete IgM in the presence of recombinant interleukin 2 (rIL 2) (10 to 50 U/ml); a concomitant increase in proliferation was observed. Recombinant interferon-gamma (rIFN-gamma) was a potent inhibitor of proliferation. In addition, rIFN-gamma did not induce an increase in IgM secretion and, when added to rIL 2-stimulated BCL1-3B3 cells, completely blocked IgM secretion at a concentration of 10 U/ml. Purified and recombinant IL 1 (rIL 1) had no significant effect on differentiation either alone or in combination with rIL 2 and/or rIFN-gamma. However, rIL 1 was able to synergize with rIL 2 in enhancing the proliferation of BCL1-3B3. The ability of cells to respond to rIL 2 was limited to the in vitro (Ly-1+) clones of BCL1 cells since the in vivo derived (Ly-1-) BCL1 cells did not differentiate in response to IL 2. Consistent with their functional response to rIL 2, cells from the in vitro clone (3B3) are IL 2-receptor-positive (IL-2R+) and the in vivo derived BCL1 cells are IL-2R-. A second set of neoplastic B cell clones derived from the AKR 225 lymphoma did not respond to rIL 2 even though they expressed receptors for IL 2 and could be induced by T cell supernatant to secrete IgM, thus indicating that expression of IL 2R is not the sole requirement for IL 2 responsiveness. The monoclonal anti-IL 2R antibody (7D4) mimicked IL 2 in its ability to stimulate differentiation of BCL1-3B3 cells. These data suggest that rIL 2 and the monoclonal anti-IL-2R antibody are capable of inducing a differentiative response in the Ly-1+ BCL1-3B3 cells that is functionally equivalent to the response evoked by the previously described lymphokine B cell differentiation factor for IgM (BCDF mu). Thus, two distinct lymphokines appear to be providing a similar signal to a clonal neoplastic B cell population. Furthermore, rIL 2 is capable of providing both a proliferative and a differentiative signal.
Induction of colony-stimulating activity (CSA) by a synthetic muramyl peptide (MDP): synergism with LPS and activity in C3H/HeJ mice and in endotoxin-tolerized mice.
Authors: Galelli A , Chedid L 
Published: December 2022

Abstract
Injection of MDP into mice induces a rapid elevation of monocyte-macrophage CSA in the serum. This effect can also be observed in LPS-hyporesponsive C3H/HeJ mice. MDP and LPS induce CSA synergistically in normal mice. In contrast to the tolerance that is rapidly observed after repeated administration of LPS, MDP does not lose its capacity of inducing serum CSA after repeated injections. Repeated daily injections of MDP also fail to induce tolerance to the LPS-CSA inducing effect. Furthermore, whereas mice rendered tolerant to LPS become hyporesponsive to many other bacteria or bacterial products, they remain responsive to MDP. These data showing that MDP can act synergistically with another CSA inducer, can be injected repeatedly, and can stimulate mice unresponsive to LPS suggest potentially important in vivo applications.
Characterization of an anti-peptide antibody that recognizes the murine analogue of the human T cell antigen receptor-T3 delta-chain.
Authors: Samelson L E , Weissman A M , Robey F A , Berkower I , Klausner R D 
Published: December 2022

Abstract
The T cell antigen receptor consists of two disulfide-linked 40,000 to 45,000 dalton glycoproteins (alpha and beta) that contain variable and constant regions analogous to those found in immunoglobulin molecules. The antigen receptor on murine T cells is noncovalently associated with four additional nonpolymorphic structures. We describe an antibody that binds one of these molecules, a 26,000 dalton glycoprotein homologous to the human T3 delta-chain. This antibody immunoprecipitates the entire antigen receptor complex from a T cell hybridoma and from normal murine thymocytes. It represents the first reagent that can immunoprecipitate the antigen receptor complex on all murine T cells.
Metabolism of 5-hydroxyicosatetraenoate by human neutrophils: production of a novel omega-oxidized derivative.
Authors: O'Flaherty J T , Wykle R L , Redman J , Samuel M , Thomas M 
Published: December 2022

Abstract
Human neutrophils incorporated 5-hydroxy-E,Z,Z,Z-6,8,11,14-eicosatetraenoic acid (5-HETE) into cellular triglyceride and phospholipid. They also metabolized 5-HETE into a novel, extracellularly released derivative, 5,20-dihydroxy-E,Z,Z,Z-6,8,11,14-eicosatetraenoic acid (5,20-diHETE). 5,20-diHETE formation predominated at higher substrate concentrations and longer incubation intervals. In the absence of added 5-HETE, 1 X 10(8) neutrophils stimulated with 20 microM ionophore A23187 produced up to 243 ng of 5,20-diHETE, indicating that both endogenously formed and exogenously added substrate could be oxidized at carbon 20. 5,20-diHETE was about 10- to 100-fold weaker than 5-HETE in enhancing human neutrophil degranulation responses to platelet-activating factor. omega-Oxidation appears to be a general enzymatic mechanism for inactivation of arachidonic acid metabolites.
Regulation of class II gene expression: analysis in B cell stimulatory factor 1-inducible murine pre-B cell lines.
Authors: Polla B S , Poljak A , Ohara J , Paul W E , Glimcher L H 
Published: December 2022

Abstract
We have analyzed the mechanism of action of BSF-1 on class II gene expression in two murine pre-B cell lines that are at different stages of differentiation. In vitro transcription assays demonstrated that BSF-1 induced rapid transcription of class II genes within 1 hr by a mechanism that was independent of protein synthesis. Although cell surface expression of class II was detectable by 2 hr after induction and persisted for up to 96 hr after removal of BSF-1, levels of class II-specific mRNA and density of cell surface class II increased to a maximum between 24 and 72 hr after induction. Furthermore, prostaglandin E2 prevented the induction of class II gene expression by BSF-1. The effects of BSF-1 are unlikely to be mediated through calcium fluxes or activation of protein kinase C, since treatment with agents such as PMA and the calcium ionophore A23187 did not result in expression of class II molecules. Other lymphokines, such as IFN-gamma, IL 1, IL 2, and IL 3, did not affect class II gene expression in these two cell lines. These data provide further insight into the mechanisms by which class II gene expression is regulated in B cells.
Potentiation of the in vitro cytotoxicity of chlorambucil by monoclonal antibodies.
Authors: Smyth M J , Pietersz G A , McKenzie I F 
Published: December 2022

Abstract
It had previously been shown by using polyclonal antibodies that chlorambucil (CBL) and antibody did not have to be covalently bound to selectively inhibit tumor cell growth. This paper has reexamined this phenomena by using monoclonal antibodies (MoAb) and has sought to determine how antibody may serve to focus and to increase the cytotoxic effect of non-covalently bound CBL. In vitro, it was shown that MoAb per se had no effect, the MoAb had to be reactive with and to bind to tumor target cells for CBL to have an enhanced cytotoxicity. Furthermore, not all MoAb were effective; IgM and IgG2a subclasses enhanced CBL cytotoxicity, but IgG3 did not. At the cell surface, studies clearly showed that endocytosis of CBL and MoAb did not occur, as metabolic inhibitors, and lowered temperatures, which both inhibit endocytosis, had no effect on their cytotoxicity. In addition, NH4Cl an inhibitor of lysosomal enzymes did not reduce the cytotoxicity of CBL and MoAb. Thus CBL that is non-covalently bound to MoAb enters the cell independently of the MoAb. We conclude therefore that cell-bound MoAb is able to concentrate CBL on the surface of tumor cells by an unknown mechanism thereby enabling CBL to selectively alkylate their cell membranes and subsequently inhibit additional tumor cell growth.
Analysis of deficiencies in IFN-gamma-mediated priming for tumor cytotoxicity in peritoneal macrophages from A/J mice.
Authors: Hamilton T A , Somers S D , Becton D L , Celada A , Schreiber R D , Adams D O 
Published: December 2022

Abstract
The functional and biochemical responses of macrophages derived from the A/J mouse strain to IFN-gamma have been studied. As compared to macrophages obtained from C57BL/6 strain mice, cells from mice of the A/J strain are deficient in their response to IFN-gamma for acquisition of tumoricidal competence. This deficiency was not due to reduced expression of surface receptors for IFN-gamma or to altered affinity of the receptor for its ligand. IFN-gamma recently has been shown to enhance the potential activity of protein kinase C (PKc) and to modulate the efflux of intracellular Ca2+ in macrophages from C57BL/6 mice. Neither of these two biochemical changes were induced in macrophages derived from A/J mice. Functional competence could, however, be pharmacologically induced in both C57BL/6- and A/J-derived macrophages by combined treatment with an ionophore plus phorbol myristic acetate, which increase intracellular Ca2+ and stimulate PKc, respectively. Although the exact nature of the deficit in A/J strain mice has not been defined, the present findings indicate that it lies between the expression of receptor and the modulation of PKc activity and Ca2+ levels. Furthermore, the data provide support for the notion that these molecular changes are important components of the stimulus-response coupling process in IFN-gamma-mediated activation of macrophages.
Correction of defective IL 3 responses of T lymphocytes from autoimmune mice.
Authors: MacNeil D , Krystal G , Fairhurst M , Waterfield J D 
Published: December 2022

Abstract
MRL-+ and MRL-lpr congenic mice differ by the presence and expression of the homozygous recessive lymphoproliferation (lpr) gene. One manifestation of this gene is a massive T cell proliferation that results in a generalized lymphadenopathy in older animals. Interleukin 3 (IL 3), a recently described lymphokine, has been shown to influence lymphocyte differentiation. It was possible that abberrant IL 3 production was the mechanism responsible for the lpr controlled lymphadenopathy. Consequently, in this paper we tested the MRL congenic mice for their ability to produce IL 3. We report that the T lymphocytes from MRL-+ and MRL-lpr could neither respond to pokeweed mitogen in the induction of proliferation nor produce IL 3. Moreover, IL 3 was not produced constitutively nor could be induced at any time period up to 5 days in vitro. This hyporesponsiveness was shown to be controlled at the accessory cell level. Addition of T cell-depleted peritoneal exudate cells from normal major histocompatibility complex (MHC) compatible mice was able to restore the ability to secrete IL 3 in response to pokeweed mitogen in MRL-+ and young MRL-lpr mice. The defect in the accessory cells could be overridden by two means: the incorporation of phorbol myristate acetate in the induction system and preincubation of the cells in tissue culture.
Psoriatic skin lesions contain biologically active amounts of an interleukin 1-like compound.
Authors: Camp R D , Fincham N J , Cunningham F M , Greaves M W , Morris J , Chu A 
Published: December 2022

Abstract
The presence of neutrophil chemoattractant material in aqueous extracts of lesional psoriatic scale has been investigated by use of an agarose microdroplet chemokinesis method in combination with ultrafiltration and high-performance liquid chromatography (HPLC). Fractions were also assayed for murine thymocyte co-stimulating activity. Aqueous extracts of psoriatic scale contained significantly greater neutrophil chemokinetic activity than extracts of scale from normal skin. Successive ultrafiltration of extracts showed that the chemokinetic material was 10 to 30 kd. Heat lability and gel filtration HPLC characteristics suggested that the major chemokinetically active material in aqueous extracts of psoriatic scale is different from C5a des arg. Reversed-phase HPLC of 0.1% trifluoroacetic acid/acetonitrile extracts of psoriatic scale revealed two clearly resolved peaks of chemokinetic activity, the major peak consistently containing thymocyte co-stimulating activity. No significant neutrophil chemokinetic activity was seen in fractions after reversed-phase HPLC of scale from normal skin. These findings suggest that a major portion of the neutrophil chemoattractant activity in aqueous extracts of psoriatic scale is due to interleukin 1-like material, which may play a role in the pathogenesis of this disease.
Compartmentalized activation of the interleukin 2 gene by lung T lymphocytes in active pulmonary sarcoidosis.
Authors: Müller-Quernheim J , Saltini C , Sondermeyer P , Crystal R G 
Published: December 2022

Abstract
Sarcoidosis is a systemic disorder characterized by the accumulation of large numbers of interleukin 2 (IL 2) releasing helper (Leu-3+) T cells in involved organs. To determine whether the IL 2 gene is activated in sarcoidosis T cells in a systemic manner or only at sites of disease, cells obtained by bronchoalveolar lavage of individuals with active sarcoidosis, inactive sarcoidosis, and normals were evaluated for the spontaneous presence of IL 2 transcripts by using a human IL 2 cDNA probe and Northern analysis of extracted RNA. Freshly recovered lung cells of individuals with active pulmonary sarcoidosis contained 0.85 kilobase pairs (kb) IL 2 mRNA transcripts. In contrast, no IL 2 mRNA transcripts could be detected in fresh autologous blood T cells or in purified autologous blood Leu-3+ T cells, although IL 2 mRNA transcripts were inducible in these cells by phytohemaglutinin/phorbol myristic acetate. The sarcoid lung T cells, however, did not express the IL 2 gene constitutively; when placed in culture with no stimulation and evaluated after 24 hr, they demonstrated down regulation of the amounts of IL 2 mRNA transcripts, despite the fact that they were capable of re-expressing the IL 2 gene and releasing more IL 2 in response to added activation signals. Thus the activation of the IL 2 gene in T cells in active sarcoidosis occurs at the sites of disease and is not a generalized property of T cells throughout the body, and is not sustained if the T cells are removed from the sites of disease. Although the cause of sarcoid is unknown, these observations are consistent with the concept that sarcoid is associated with local stimuli at the site of disease eliciting the Leu-3+ T cell IL 2 gene activation that plays such a critical role in the pathogenesis of this disease.
Interaction of IL 1 and TPA in modulation of eosinophil function.
Authors: Pincus S H , Whitcomb E A , Dinarello C A 
Published: December 2022

Abstract
The tumor co-promotor TPA is believed to enhance a wide variety of cellular processes by interacting with protein kinase C. Interleukin (IL 1) is a family of highly active molecules which augments the host response to infection. We have explored the interactions of these activators of cell function on the modulation of selected eosinophil functions. The effects of purified monocyte-derived IL 1 on the eosinophil functions of oxidative metabolism (as measured by superoxide anion production) and degranulation (as measured by release of the granular enzymes arylsulfatase and beta-glucuronidase) have been examined. Superoxide anion production by eosinophils stimulated with standard doses of the stimulant phorbol myristic acetate (TPA) (1 microgram/ml) was augmented approximately 20% by preincubation with IL 1. However, IL 1 alone had no effect on superoxide anion production. At suboptimal doses of TPA, there was a dose-dependent inhibition of superoxide anion production in the presence of IL 1. Calcium ionophore (2 X 10(-7) M) markedly enhanced superoxide anion production elicited by 0.1 ng/ml of TPA, but had only modest effects in the absence of TPA. When IL 1 was added to eosinophils stimulated by TPA in the presence of calcium ionophore, there was a dose-dependent increase in superoxide anion production. In contrast to other cell types, degranulation as measured by the release of arylsulfatase and beta-glucuronidase was not elicited by the addition of TPA (1 microgram/ml). Although calcium ionophore (2 X 10(-6) M) caused enzyme release (24.2% release of beta-glucuronidase, 29.4% release of arylsulfatase), this release was inhibited by the addition of TPA. The addition of IL 1 alone caused an approximate twofold increase in enzyme release, but pretreatment with IL 1 (1 U) reduced ionophore-mediated degranulation (p less than or equal to 0.05). Studies employing purified monocyte IL 1 were confirmed by recombinant IL 1-beta. These studies demonstrate for the first time that eosinophil function is modulated by IL 1. IL 1 may also modify the response of eosinophils to other stimuli such as ionophore and TPA. Because TPA is known to act by direct binding to protein kinase C, these studies also demonstrate that, in eosinophils, activation of protein kinase C by phorbol esters may augment one cellular function (oxidative metabolism) while inhibiting another cellular function (degranulation). Similarly, phorbol esters may act synergistically with calcium ionophore in regulation of one function (oxidative metabolism) and act antagonistically with another function (degranulation). The concept that IL 1 uniformly enhances cell function may need to be re-evaluated.
Astrocyte-derived interleukin 3 as a growth factor for microglia cells and peritoneal macrophages.
Authors: Frei K , Bodmer S , Schwerdel C , Fontana A 
Published: December 2022

Abstract
Astrocytes have been shown to release an interleukin 3 (IL 3)-like factor that induces the expression of 20-alpha-hydroxysteroid-dehydrogenase (20-alpha SDH) in nu/nu spleen cells, and the proliferation of the IL 3-dependent cell line 32DCL. We have investigated whether astrocyte-derived IL 3 supports growth of macrophages and their representatives in the brain, the microglia cells. Evidence for intercellular communication between murine astrocytes and macrophages became already detectable in co-culture experiments: astrocytes activated with endotoxin resulted in an increased growth of peritoneal macrophages on the astrocyte monolayer. Biochemical analysis of supernatants of activated astrocytes revealed that the IL 3-like factor that stimulated 32DCL cells and the expression of 20 alpha SDH also served as a growth factor for cultured peritoneal macrophages. The same results were obtained by using microglia cells isolated from primary brain cell cultures of newborn mice, which are characterized by their positive reaction for macrophage markers such as Mac-1 and nonspecific esterase. If secreted by reactive astrocytes in vivo, the IL 3-like factor may contribute to the accumulation of macrophages and microglia cells detected in brain lesions of patients with multiple sclerosis.