bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration of Leishmania donovani infection levels by selective impairment of macrophage signal transduction.
Authors: Moore K J , Labrecque S , Matlashewski G 
Published: December 2022

Abstract
Leishmania donovani is an obligate intracellular protozoan which residues and multiples in macrophages. The molecular basis for this host-parasite interaction is poorly understood. Targeting a signal transduction pathway in the macrophage would allow this parasite to manipulate cellular gene expression, and this may aid in ensuring its survival. We demonstrate that in macrophages infected with L. donovani for 18 h, c-fos gene expression mediated through protein kinase A was unaffected under conditions where there was an impairment of protein kinase C (PKC)-mediated c-fos gene expression. This selective impairment of PKC-mediated c-fos gene expression was substantially augmented in macrophages put in contact with L. donovani promastigotes or amastigotes for only 1 h. Treatment of macrophages with L. donovani-conditioned media was not sufficient to significantly impair signal transduction. These data revealed that L. donovani selectively impaired the transmission of information from the cell surface to the nucleus and that this effect is induced very soon after macrophage-parasite contact. The biologic significance of this altered signal transduction in the macrophage with respect to infection with L. donovani was then examined by treating macrophages with various protein kinase inhibitors prior to infection with amastigotes. Macrophages that were treated with PKC inhibitors demonstrated an increase in the initial uptake of the parasite and carried heavier infection levels than did controls. In contrast, treatment of macrophages with an inhibitor of calmodulin-dependent protein kinase (CaM-PK) did not show significant differences in the initial uptake of parasite, but prolonged impairment of CaM-PK resulted in a decrease in the level of macrophage infection. Further experiments revealed that promastigote proliferation was severely impaired by the CaM-PK inhibitor but not any of the other inhibitors.
Mechanistic differences between migration inhibitory factor (MIF) and IFN-gamma for macrophage activation. MIF and IFN-gamma synergize with lipid A to mediate migration inhibition but only IFN-gamma induces production of TNF-alpha and nitric oxide.
Authors: Herriott M J , Jiang H , Stewart C A , Fast D J , Leu R W 
Published: December 2022

Abstract
Previously we found that murine macrophage migration inhibition (MMI) was mediated by IFN-gamma-priming and lipid A triggering. With the recent availability of human recombinant migration inhibitory factor (MIF), which is distinctly different from IFN-gamma and other cytokines, we have now attempted to explore possible mechanistic differences between IFN-gamma and MIF to mediate MMI. Neither MIF not IFN-gamma were active alone, but effectively primed murine inflammatory macrophages for subsequent triggering by lipid A to mediate MMI. A specific neutralizing antibody for rMIF abrogated MMI mediated only by MIF and not by IFN-gamma-primed macrophages. Distinct differences were also found between the mechanisms by which MIF and IFN-gamma synergized with lipid A for activation in that IFN-gamma-primed and lipid A triggered macrophages produced TNF and nitric oxide (NO), whereas MIF-primed cells did not. Macrophages primed with IFN-gamma and triggered by rTNF were inhibited in their migration, whereas MIF failed to synergize with rTNF for MMI. An inhibitor of NO production NG-monomethyl-L-arginine inhibited MMI mediated by higher activating concentrations of lipid A and by IFN-gamma-primed and lipid A triggered macrophages, but had no effect on MIF-primed cells in concert with lipid A for increased expression of both TNF-alpha mRNA and NO synthase mRNA. Taken together, our results indicate that both MIF and IFN-gamma prime macrophages to synergize with lipid A to mediate MMI but by different mechanisms. The activation process by IFN-gamma to mediate migration inhibition appears to resemble requirements for rendering macrophages tumor cytotoxic in the production of TNF for autocrine-mediated NO generation by primed macrophages. In contrast, MIF-mediated MMI was independent of requirements for either TNF or NO production.
Modulation of lipopolysaccharide-induced cytokine gene expression in mouse bone marrow-derived macrophages by muramyl dipeptide.
Authors: Le Contel C , Temime N , Charron D J , Parant M A 
Published: December 2022

Abstract
Previous studies have shown that an i.v. injection of muramyl dipeptide (MDP) before a LPS challenge strongly potentiated serum TNF and IL-6 release in mice. Therefore the direct action of MDP was examined on TNF-producing cells, namely in macrophages stimulated or not by LPS. The level of TNF-alpha, IL-1 alpha, and IL-6 mRNA was determined in bone marrow-derived macrophages (BMM). A marked TNF-alpha mRNA accumulation was found between 1 and 6 h after stimulation with MDP or LPS. LPS-induced IL-1 alpha mRNA transcript was delayed (3 h) than those after MDP induction (1 h). Conversely, kinetic induction of the IL-6 mRNA transcript was delayed in MDP-treated BMM as compared with LPS-stimulated cells. MDP pretreatment of BMM for 3 h not only enhanced the total level of LPS-induced TNF-alpha, IL-1 alpha, and IL-6 mRNA (respectively 2.9-, 1.6-, and 2.4-fold increase), but it also delayed the kinetics of IL-1 alpha and IL-6 species accumulation. The enhancement induced by MDP pretreatment at the level of cytokine mRNA accumulation was correlated with an increase in LPS-induced TNF and IL-6 biologic activity production in supernatant fluids. In addition, in BMM from C3H/Hej mice MDP pretreatment enhanced the weak effect of LPS on TNF mRNA transcript accumulation and was required to produce LPS-induced TNF bioactivity. Our results suggest that MDP and LPS could act through distinct pathway(s) to induce cytokine gene expression. Moreover, the priming effect displayed by MDP could result in modulation of the LPS-induced cytokine gene expression at the transcriptional and/or post-transcriptional level.
Calcium mobilization-associated and independent cytosolic acidification elicited in tandem with Na+/H+ exchanger activation in target cell-adherent human NK cells.
Authors: Edwards B S , Hoffman R R , Curry M S 
Published: December 2022

Abstract
Flow cytometry was used to identify mechanisms by which human NK cells regulate intracellular pH (pHi) and to investigate the relationship between NK cell pHi and cytolytic function. Temporally resolved determinations of pHi were simultaneously made in NK cells that formed conjugates with target cells (NKC) and unconjugated NK cells (NKU) on the basis of the red/orange fluorescence emission ratio of the pH indicator seminapthylrhodafluor-1. Two pHi regulatory mechanisms were identified in NK cells: 1) a HCO3-/Cl- antiport that promoted pHi changes in response to variation of extracellular HCO3- and Cl- but not Na+ ion concentrations, was sensitive to stilbene derivatives 4,4'-diisothiocyanatostilbene sulfonic acid and 4-acetamido-4'-isothyocyanotostilbene-2-2'-disulfonic acid, and exhibited similar activity in NKC and NKU, and 2) a Na+/H+ exchanger that promoted pHi changes in response to extracellular Na+ ion concentration changes and was sensitive to dimethylamiloride (DMA), permeable to Na+ and Li+ but not K+ or N-methyl-D-glucamine, and quiescent in NKU but activated in target cell-adherent NKC. When Na+/H+ exchange was blocked with 10 microM DMA, the pHi of NKC bound to NK-sensitive K562 target cells progressively decreased for 3 to 4 min, then stabilized at 0.1 to 0.15 pH units below the pHi of NKU. A significant temporal decline in NKC pHi also occurred in the nominal absence of extracellular Ca2+ (0.07 +/- 0.02 pH units) and when NKC formed conjugates with NK-resistant B lymphoblastoid target cells that failed to mobilize NK cell Ca2+ (0.07 +/- 0.01 pH units) (mean +/- SD). However, the magnitude of the NKC cytosolic acidification response was consistently reduced (42 +/- 4 and 44 +/- 6%, respectively) under these Ca2+ flux response-limiting conditions. Thus, adhesion to target cells triggered two pHi-related responses in NK cells: 1) a decline in pHi which exhibited both Ca2+ mobilization-dependent and -independent components, and 2) Na+/H+ exchanger activation by which acid production was neutralized. Manipulations of HCO3- and DMA that clamped NKC pHi at values ranging from 6.8 to 7.2 failed to significantly influence NK cell cytolytic function. By contrast, isosmotic replacement of extracellular Na+ with NMDG resulted in a 57 +/- 22% inhibition of NK cell-mediated cytolysis (n = 8, p &lt; 0.01). NKC pHi declined to 6.8 to 6.9 under these conditions, but this was not the apparent basis of impaired cytolysis because sustained elevation of NKC pHi by addition of dimethylamine failed to significantly reverse inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)
Large cytoplasmic inclusion body kappa-chain has unusual intrachain disulfide bonding.
Authors: Jäck H M , Sloan B , Grisham G , Reason D , Wabl M 
Published: December 2022

Abstract
The Ig kappa L chain synthesized by the mouse hybridoma line F10 forms large fibrils in the lumen of the endoplasmic reticulum. Despite the formation of these inclusion bodies, free kappa-chain is secreted. Both intracellular and secreted kappa-chains in this line migrate faster on SDS gels; thus, the F10 kappa-chain seems to be more compact than normal Ig L chain. In normal kappa-chain, four cysteine residues form intrachain disulfide bonds and the fifth connects the L chain to the H chain. Although the five cysteine residues of the aberrant kappa-chain are in the normal positions, they display an unusual gel pattern when the intrachain disulfide bonds are opened with 2-ME; that is, the intrachain disulfide bonding pattern of F10 kappa-chain seems to be unusual. It is suggested that the abnormal folding pattern favors fibril formation.
Nitric oxide-mediated apoptosis in murine peritoneal macrophages.
Authors: Albina J E , Cui S , Mateo R B , Reichner J S 
Published: December 2022

Abstract
Nitric oxide (NO) synthase, the enzyme responsible for the generation of the cytotoxic compound NO from L-arginine, is induced in macrophages during activation. Previous work demonstrated that the cytotoxicity of NO extends to the macrophages that produce it, because the activity of NO synthase in these cells correlates inversely with their life span in culture. Data presented here demonstrate that the NO-dependent death of murine peritoneal macrophages activated in vitro with IFN-gamma and LPS is mediated through apoptosis. Evidence in this direction was provided by microscopic examination of the cells, which revealed the presence of nuclear and cytoplasmic alterations characteristic of apoptosis, and by the specific pattern of internucleosomal DNA fragmentation detected by electrophoresis. That these alterations resulted from the production of NO was confirmed by the preventive effects of cell activation in L-arginine-restricted medium or in medium containing an inhibitor of NO synthase, NG-monomethy L-arginine, and more directly by the induction of apoptosis by exposure of the cells to authentic NO gas. Additional results demonstrated that glucose starvation, the inhibition of the tricarboxylic acid cycle with fluorocitrate or of glycolysis with iodoacetate, but not the suppression of the electron transport chain with potassium cyanide, also induced macrophage apoptosis. The potential role of metabolic inhibition as a mechanism for NO-mediated apoptosis, as well as the relationship of these findings with events occurring in wounds and other sites of macrophage infiltration are discussed.
Short time exposure to lipopolysaccharide is sufficient to activate human monocytes.
Authors: Gallay P , Jongeneel C V , Barras C , Burnier M , Baumgartner J D , Glauser M P , Heumann D 
Published: December 2022

Abstract
Very little is known about early events in LPS binding and about the duration of LPS exposure required to activate monocytes. In the present study, we have investigated the kinetics of LPS binding to human monocytes and the time of exposure required to trigger the synthesis of TNF-alpha. We directly followed the binding of FITC-labeled LPS to monocytes by flow cytometry or confocal laser microscopy. LPS was able to bind to the cell surface within 1 min of exposure, and was internalized within 5 min. Equilibrium was reached within 15 min at all but the lowest LPS concentration tested (10 ng/ml). Binding was dependent on the presence of LPS-binding protein, supplied either as a plasma component or in purified form, and inhibited by an anti-CD14 mAb (MY4). Polymyxin B, an inhibitor of LPS-mediated activation, essentially abrogated the LPS-binding protein- and CD14-dependent binding of LPS to monocytes. Using either the anti-CD14 mAb or polymyxin B to block further LPS binding, we found that 5 to 10 min of exposure was sufficient to trigger maximal TNF-alpha release. Similarly, monocytes washed after 5 to 15 min exposure to eliminate LPS also produced high levels of TNF-alpha transcripts without further presence of LPS in the medium. We conclude that a few minutes of exposure to physiologically relevant concentrations of LPS are sufficient to trigger both maximal binding and activation of monocytes.
Cytokine mediation of the suppressive effect of ferritin on colony-stimulating factor-1-dependent monocytopoiesis.
Authors: Kreisberg R , Detrick M S , Osmand A P , Moore R N 
Published: December 2022

Abstract
Peptide-specific IgG from a rabbit immunized with an alanine-lysine-proline-arginine ((ALA1)-tuftsin) containing 14-mer "ferritin" peptide neutralized rat liver ferritin inhibition of in vitro CSF-1-dependent monocytopoiesis. Antiferritin IgG similarly neutralized the inhibitory effect of ferritin but did not neutralize peptide inhibition of the in vitro myelopoietic response. No cross-reactivity between the respective antibodies and Ag was detected either by Western immunoblot or by competitive ELISA. Depletion of adherent cells before marrow cell culture significantly reduced the inhibitory effect of ferritin but did not influence peptide inhibition of CSF-1-stimulated colony formation. Adherent marrow cells and P388D1 cells treated with both CSF-1 and ferritin, but not either alone, produced inhibitory supernatant culture media that were neutralized by antipeptide but not antiferritin IgG. High resolution molecular sieve chromatography of the inhibitory adherent marrow cell and P388D1 supernatants resolved two peaks of 50 to 60 kDa and approximately 30 kDa in each. The inhibitory activity in all four peaks was neutralized by antipeptide but not antiferritin IgG. The ferritin/CSF inhibitors were not further characterized although identity with IL-6, IL-8, TNF-alpha, transforming growth factor-beta, and IFN-alpha/beta could be eliminated. The results indicate that ferritin inhibition of CSF-1-dependent monocytopoiesis is mediated by an endogenously produced inhibitor, or inhibitors, that shares antigenic similarity with the (ALA1)-tuftsin-containing 14-mer peptide and that adherent marrow cells, most likely monocytes or macrophages, produce the endogenous inhibitors in response to both CSF-1 and ferritin.
Impairment of function in aging neutrophils is associated with apoptosis.
Authors: Whyte M K , Meagher L C , MacDermot J , Haslett C 
Published: December 2022

Abstract
Neutrophil apoptosis or programmed cell death permits neutrophil recognition and ingestion by macrophages and represents a mechanism capable of promoting resolution of inflammation. The consequences of apoptosis for neutrophil function are the subject of these investigations. A direct relationship between apoptosis and loss of cytoskeletal functions, phagocytosis, degranulation, and respiratory burst was demonstrated by counterflow centrifugation of neutrophils (aged for 24 h in culture) into fractions with varying proportions of apoptosis. Apoptotic neutrophils displayed a loss of background functions: ability to spread and change shape and random migration. They also showed a reduced ability to respond to deliberate stimulation with the receptor-dependent stimulus, FMLP, by undergoing shape change, chemotaxis, degranulation, and respiratory burst, and showed an inability to phagocytose opsonized zymosan. Loss of FMLP binding to apoptotic neutrophils was demonstrated by analysis of FML[3H]P binding and by autoradiography. Superoxide anion production, but not shape change or degranulation response, to the receptor-independent stimulus, PMA, was preserved in apoptotic neutrophils, implying some retention of intracellular signaling pathways relevant to superoxide production. Apoptosis thus marks a loss of neutrophil functional responsiveness and defines the cell as effectively "isolated" from its external milieu. Neutrophil apoptosis may represent an important event in the control of inflammation, marking the neutrophil both for disposal and as a cell with profound loss of its capacity to generate and release histotoxic products on external stimulation.
Topical application of T-2 toxin inhibits the contact hypersensitivity response in BALB/c mice.
Authors: Blaylock B L , Kouchi Y , Comment C E , Pollock P L , Luster M I 
Published: December 2022

Abstract
T-2 toxin, a trichothecene mycotoxin, has previously been shown to alter immune functions and promote skin tumors. We demonstrate that topically applied T-2 toxin reduces the ear swelling response to oxazolone challenge in BALB/c mice. For this reduction in ear swelling to occur, toxin application must be at, or within, 1 h after challenge. Dose-response studies showed a 44% reduction in ear swelling with 30 ng of T-2 toxin as compared with a similar reduction with 300 ng of dexamethasone. T-2 toxin did not affect Ag transport from the challenge site to the draining lymph nodes as measured by FITC transport. However, T-2 toxin significantly reduced both MHC class II (Ia) expression and Ag presentation at the same concentrations. Because T-2 toxin, a known protein synthesis inhibitor, was found to inhibit protein synthesis in epidermal cell cultures as measured by [3H]-leucine incorporation, cycloheximide was also examined. Cycloheximide reduced both oxazolone-induced ear swelling and Ag presentation in a similar manner to T-2 toxin. One mechanism of action for T-2 toxin in reducing the contact hypersensitivity response is via inhibition of protein synthesis and effective Ag presentation by epidermal Langerhans cells. This may involve alterations in Ia Ag expression, although a role for class II in the induction phase of the contact hypersensitivity response has not been established definitively.
Correlation of oncostatin M secretion by human retrovirus-infected cells with potent growth stimulation of cultured spindle cells from AIDS-Kaposi's sarcoma.
Authors: Radka S F , Nakamura S , Sakurada S , Salahuddin S Z 
Published: December 2022

Abstract
Oncostatin M (OM), a 30-kDa glycoprotein, recently was identified as a major growth-promoting factor in the conditioned medium (CM) of the 38-0 cell line, a CD4,+ chronically human T lymphotropic virus type (HTLV)-II-infected, transformed T cell line. CM 38-0 induced the proliferation of spindle cells cultured in vitro from AIDS-associated Kaposi's sarcoma (AIDS-KS) cells. To determine how much of the AIDS-KS cell growth activity present in 38-0 CM was because of the presence of OM, we depleted OM by using specific mAb-affinity chromatography. OM purified from this CM stimulated AIDS-KS cell growth in a concentration-dependent fashion. The effluent, completely depleted of OM, failed to induce growth of AIDS-KS cells. To detect the constitutive release of OM by cells acutely or chronically infected with either HTLV-I, HTLV-II, or HIV-1, we utilized an enzyme-linked immunoassay. Whereas the chronically infected cells released significant levels of OM, the acutely infected cells released little or no OM. The presence of OM in HIV-1-infected T-cell CM correlated completely with AIDS-KS cell growth activity. Infrequently, low level AIDS-KS cell growth activity was seen in the absence of OM. This correlated with relatively high levels of IL-6 in the CM. In a CM-containing OM in the absence of detectable IL-6, a neutralizing antibody to OM completely abrogated KS cell growth activity. The presence of specific oncostatin M receptors on the KS cell lines was confirmed by cross-linking experiments. The results shown here suggest that T cells chronically infected with HIV-1 can secrete OM, which may play a role in the initiation or progression of AIDS-KS lesions, either alone, or in concert with IL-6.
Dissection of the function of HLA class II and costimulation in B cell-mediated and toxic shock syndrome toxin-1-induced T cell proliferation.
Authors: Dennig D , O'Reilly R J 
Published: December 2022

Abstract
In this study we have demonstrated that costimulation for TSST-1-induced T cell proliferation is provided by HLA class II negative accessory B cells. In addition, TSST-1 binding to these HLA class II negative accessory B cells could not be detected by immunocytofluorescence, or in a system in which T cell proliferation depended on TSST-1 pretreated HLA class II negative B cells. These findings suggest that accessory signals can be supplied by B cells that are not involved in the activation of T cells via Ag-HLA/TCR-CD3 complex interaction: TCR ligation by a TSST-1/HLA complex and costimulation need not be delivered by the same cell. In the presence of HLA class II negative B cells, T cell proliferation in response to TSST-1 could be achieved despite addition of a mAb that can block HLA class II binding sites for TSST-1. These findings suggest the possibility that TSST-1 may directly ligate TCR. In the presence of anti-BB1-treated HLA class II negative accessory cells, TSST-1-induced T cell proliferation was inhibited by over 50% indicating the involvement of the BB1/CD28 pathway. The leukemic pre-B cell lines NALM-6, and BLIN-1, both of which express surface HLA class II Ag, but not the costimulatory B cell activation Ag BB1, were deficient in their accessory function for T cell proliferation in response to the superantigen TSST-1 and the mitogen Con A.
Characterization of a novel cell-surface molecule expressed on subpopulations of activated T and B cells.
Authors: Laszlo G , Hathcock K S , Dickler H B , Hodes R J 
Published: December 2022

Abstract
A mAb, GL7, is described that reacts with a 35-kDa protein on subsets of activated mouse B cells as well as activated CD4+ and CD8+ peripheral T cells. In normal mice analyzed by flow cytometry, GL7 bound at low surface density to 0 to 9% of splenic B cells and 0 to 1% of splenic T cells. In contrast, GL7 bound at high density to a subpopulation comprising approximately 20% of TCR-bright thymocytes, and to B220+ cells in the bone marrow. The activation of B cells by various stimuli resulted in high levels of expression of the surface molecule identified by GL7 on up to 70% of B cells after 48 h; the remaining B cells expressed low or undetectable levels of this molecule, despite evidence of other activation-specific changes in cell-surface phenotype. The GL7-positive population of B cells induced by IL-5 stimulation exhibited high levels of both proliferative and IgM secretory activity, whereas the GL7-negative population showed little of either activity. Activation of splenic T cells with Con A for 48 h resulted in the expression of this determinant at high density on both CD4+ and CD8+ cells. GL7 thus appears to identify a previously uncharacterized cell-surface molecule expressed selectively on subpopulations of activated B and T cells as well as on discrete subpopulations of T and B lineage cells in vivo.