bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of activin A in negative regulation of normal and tumor B lymphocytes
Authors: Zipori Dov , Barda-Saad Mira 
Published: September 2022

AbstractActivin A, a member of the transforming growth factor β superfamily, has a wide spread expression pattern and pleiotropic functions. In thisoverview we summarize data that points to a role of activin A innegative regulation of B lineage lymphocytes. Experiments performed byus and by other groups revealed the capacity of activin A to causeapoptotic death of tumor myeloma cells, through mechanisms of cellcycle inhibition and antagonism with the survival signal ofinterleukin-6. In vitro studies on B lymphocyte generation from bonemarrow stem cells and use of human nasal polyps as a model of inflamedtissue further demonstrate an inhibitory role of activin A in B cellspread and accumulation. These data are analyzed with respect to ourmodel of tissue organization that we term the “restrictin model ofcell growth regulation.” This model assumes a morphogen-like role ofactivin A in the hematopoietic system. Thus, the relative concentrationof biologically functional activin A, in different parts of the tissue, may determine the local B cell content and functional state of thesecells within a specific microenvironment.
Tissue distribution of CD6 and CD6 ligand in cattle: expression of the CD6 ligand (CD166) in the autonomic nervous system of cattle and the human
Authors: Konno A , Ahn J-S , Kitamura H , Hamilton M J , Gebe J A , Aruffo A , Davis W C 
Published: September 2022

AbstractWe studied the tissue distribution of CD6+ lymphocytes and cells expressing the CD6 ligand (also known as activated leukocyte cell adhesion molecule CD166) in calves by immunohistochemistry using an anti-bovine CD6 monoclonal antibody (mAb), a human CD6 (huCD6)-immunoglobulin G1 fusion protein (huCD6-Ig), and an anti-human CD166 (anti-huCD166) mAb. The huCD6-Ig and anti-huCD166 mAb bound to the sympathetic and parasympathetic nerve fibers but not to myelinated nerve fibers in the spinal nerve. Studies with human tissue using the anti-huCD166 mAb yielded identical patterns of labeling. Dense accumulations of CD6+ lymphocytes were present in areas of the thymuses and spleens of calves, in areas innervated by huCD6-Ig+ nerves. The cDNAs encoding the bovine CD166 and CD6 were isolated from the sympathetic ganglion and spleen, respectively. Predicted amino acid residues that are important for human and mouse CD6-CD166 binding were also conserved in bovine CD6 and CD166. Bovine CD166 transcripts were detected by reverse transcriptase-PCR in all the tissues that bound huCD6-Ig. These results show that the bovine orthologue of CD166 was constitutively expressed in the autonomic nervous systems of cattle and suggest that CD6+ lymphocytes adhere to CD166+ autonomic nerve terminals via CD6.
Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation
Authors: Wong Birming , Lumma William C , Smith Anthony M , Sisko John T , Wright Samuel D , Cai Tian-Quan 
Published: September 2022

AbstractMacrophages secrete matrix metalloproteinase 9 (MMP-9), an enzyme that weakens the fibrous cap of atherosclerotic plaques, predisposing them to plaque rupture and subsequent ischemic events. Recent work indicates that statins strongly reduce the possibility of heart attack. Furthermore, these compounds appear to exert beneficial effects not only by lowering plasma low-density-lipoprotein cholesterol but also by directly affecting the artery wall. To evaluate whether statins influence the proinflammatory responses of monocytic cells, we studied their effects on the chemotactic migration and MMP-9 secretion of human monocytic cell line THP-1. Simvastatin dose dependently inhibited THP-1 cell migration mediated by monocyte chemoattractant protein 1, with a 50% inhibitory concentration of about 50 nM. It also inhibited bacterial lipopolysaccharide-stimulated secretion of MMP-9. The effects of simvastatin were completely reversed by mevalonate and its derivatives, farnesylpyrophosphate and geranylgeranyl pyrophosphate, but not by ubiquinone. Additional studies revealed similar but more profound inhibitory effects with L-839,867, a specific inhibitor of geranylgeranyl transferase. However, α-hydroxyfarnesyl phosphonic acid, an inhibitor of farnesyl transferase, had no effect. C3 exoenzyme, a specific inhibitor of the prenylated small signaling Rho proteins, mimicked the inhibitory effects of simvastatin and L-839,867. These data supported the role of geranylgeranylation in the migration and MMP-9 secretion of monocytes.
Differences in splenic B-lymphocyte ganglioside expression and accessibility in normal and endotoxin-hyporesponsive mice
Authors: Berenson Charles S , Rasp Robin H , Gau Jen-Tzer , Ryan John L , Yohe Herbert C 
Published: September 2022

AbstractEndotoxin-responsive (C3H/HeN) and -hyporesponsive (C3H/HeJ) murine Blymphocytes purified by adherence to anti-immunoglobulin (“antibodypanning”) possess identical gangliosides but different gangliosidesurface accessibilities. We investigated the distribution and surfaceaccessibility of gangliosides of B lymphocytes purified by adherence toplastic (“plastic panning”) or by subtraction of non-B-lymphocytecomponents. As with antibody panning, there were no entirely new orabsent gangliosides in plastic-panned or subtraction-purified Blymphocytes of each strain. However, striking changes in relativeexpression of five gangliosides were detected with each purificationprotocol. Moreover, five gangliosides of antibody-panned andplastic-panned B lymphocytes but only two gangliosides ofsubtraction-purified B lymphocytes were inaccessible to surfacelabeling. Unlike the situation for antibody-panned B lymphocytes, nointerstrain (HeN vs. HeJ) surface accessibility differences existed ingangliosides of plastic-panned or subtraction-purified cells. Exposureof subtraction-purified B lymphocytes to anti-immunoglobulin failed toelicit changes in ganglioside expression. Murine B lymphocytes havedistinct protocol-dependent differences in glycolipid phenotypewhich likely denote individual subpopulations.
Proinflammatory properties of the human S100 protein S100A12
Authors: Yang Zheng , Tao Tony , Raftery Mark J , Youssef Peter , Di Girolamo Nick , Geczy Carolyn L 
Published: September 2022

AbstractS100 proteins represent a new class of chemoattractants. Here we extend earlier evidence for the proinflammatory properties of human S100A12. A12 induced migration of monocytoid cells, with optimal activity at 10−10 M and potency of &gt;10−9 M C5a. Neutrophils were poorly responsive, and lymphocyte migration was not affected. Actin polymerization in monocytoid cells was accompanied by a sustained [Ca2+]i flux of a magnitude comparable with C5a. A12 elicited a transient infiltration of neutrophils (4–8 h) and more delayed recruitment of monocytes (8–24 h) in vivo. A12 (∼70 nM) was present in synovial fluid (SF) from rheumatoid arthritis patients, and synovium contained A12-positive neutrophils in the sublining and interstitial region, often surrounding the perivasculature but rarely in the synovial lining layer, although some macrophages were positive. The A12 gene was transiently up-regulated in monocytes by tumor necrosis factor α (6 h); induction by lipopolysaccharide (LPS) was sustained (12–48 h). A12 may contribute to leukocyte migration in chronic inflammatory responses.
Immunostimulatory CpG-modified plasmid DNA enhances IL-12, TNF-α, and NO production by bovine macrophages
Authors: Shoda Lisl K M , Kegerreis Kimberly A , Suarez Carlos E , Mwangi Waithaka , Knowles Donald P , Brown Wendy C 
Published: September 2022

AbstractThe immunogenicity of DNA vaccines is partially attributable to the adjuvant properties of bacterial plasmid DNA (pDNA) for B lymphocytes and professional antigen-presenting cells. In mice, modification of immunostimulatory sequences (ISSs), including CpG motifs, in pDNA vectors or oligodeoxynucleotides can increase or decrease their adjuvant properties. ISSs that stimulate optimal responses reportedly differ for murine and human leukocytes. We have previously characterized the mitogenic properties of oligodeoxynucleotides containing one AACGTT motif for bovine B lymphocytes. We now define cytokine responses by macrophages stimulated with pDNA engineered to contain an ISS comprising two AACGTT motifs. Macrophages activated with CpG-modified pDNA secreted significantly more interleukin-12, tumor necrosis factor-α, and nitric oxide than macrophages stimulated with unmodified pDNA or modified pDNA that contained nucleotides scrambled to remove CpG motifs. Engineered CpG-pDNA or CpG-oligodeoxynucleotides should be useful as vaccines or adjuvants to promote the enhanced type 1 responses important for protection against intracellular pathogens.
Transmembrane proteases in focus: diversity and redundancy?
Authors: Bauvois Brigitte 
Published: September 2022

AbstractRecent advances have led to the identification and characterization of an array of transmembrane proteases that mediate the proteolysis of various substrates (including bioactive peptides, components of the extracellular matrix, and integral proteins) and cell-cell or cell-matrix adhesion. The membrane proteases known to participate in these processes currently include the ectopeptidases, the membrane-type matrix metalloproteases (MT-MMPs), the ADAM (a disintegrin and metalloprotease) family, the meprins, and the secretases, and this list may be expected to grow. The roles that these molecules play within neoplastic and inflammatory sites are being investigated actively. The capacity of these ectoenzymes to transmit intracellular-transduction signals through the plasma membrane has to be considered. An appreciation of their functional redundancy is emerging.
Signaling pathways initiated in macrophages after engagement of type A scavenger receptors
Authors: Coller Susan P , Paulnock Donna M 
Published: September 2022

AbstractScavenger receptors are macrophage cell surface molecules associated with endocytic uptake of lipoproteins and binding of microbial ligands. Macrophage class A scavenger receptors (SR-As) interact with ligands to induce cellular signaling leading to gene transcription and cytokine release. We used inhibitors of early and late signaling to block SR-A-mediated polyinosinic-polycytidilic acid (poly I:C) and lipoteichoic acid (LTA) activation of RAW 264.7 macrophages. Effects of multiple inhibitors on tumor necrosis factor (TNF)-α release were monitored to determine requirements for inflammatory cytokine production. Cycloheximide, monodansylcadaverine, and cytochalasin B all blocked TNF-α release from macrophages stimulated with LTA or poly I:C, whereas monensin only nominally reduced TNF-α production. Selected inhibitors of downstream signaling events reduced SR-A-dependent TNF-α release by &gt;95% after stimulation with either ligand, whereas others were ineffective. The PKC inhibitor H7 reduced LTA-dependent secretion of TNF-α by 94% but inhibited poly I:C-dependent TNF-α production only by 50%. Priming of RAW 264.7 cells with interferon-γ potentiated the response to poly I:C but did not alter inhibitor effects. These results demonstrated that for both ligands tested here, early events of receptor internalization are requisite for cellular activation. The response pattern suggests that tyrosine phosphorylation and activation of the MAP kinase pathway are key components of SR-A-mediated signal transduction cascades.
Identification and comparison of residues critical for cell-adhesion activities of two neutrophil CD66 antigens, CEACAM6 and CEACAM8
Authors: Kuroki Motomu , Abe Hironori , Imakiirei Takayuki , Liao Shaoxi , Uchida Hiroko , Yamauchi Yasushi , Oikawa Shinzo , Kuroki Masahide 
Published: September 2022

AbstractCEACAM6 (CD66c) and CEACAM8 (CD66b) are cell-adhesion proteins onneutrophils that belong to the human carcinoembryonic antigen (CEA)family. CEACAM6 reveals homophilic adhesion and heterophilic adhesionto other CEACAM family antigens including CEACAM8, CEACAM1, and CEA, whereas CEACAM8 exhibits only heterophilic adhesion to CEACAM6. Here, we investigated and compared structural requirements for the homophilicadhesion of CEACAM6 and heterophilic adhesion between CEACAM6 andCEACAM8 at the amino acid level by using CHO transfectants expressingtheir mutant and chimeric proteins. The NH2-terminal domain(N-domain) of CEACAM6 expressed on a CHO cell was suggested to bind the N-domain of CEACAM6 or CEACAM8 on the opposing cell. Byhomologue-scanning mutagenesis, we found that the locations of thesequences critical for the adhesion of CEACAM6 to itself and to CEACAM8are overlapped and that they are highly similar but not identical tothe locations of the residues previously shown to be essential for thebinding of CEACAM antigens to Opa proteins of pathogenicNeisseriae. Our findings imply that subtle differences inthe N-domain sequences determine the specificity of the CEACAM antigenson neutrophils for interaction with the same or different CEACAMantigens and the bacterial proteins.
Increased CCR4 expression in active systemic lupus erythematosus
Authors: Hase Kayoko , Tani Kenji , Shimizu Teruki , Ohmoto Yasukazu , Matsushima Kouji , Sone Saburo 
Published: September 2022

AbstractCC chemokine receptor (CCR)4 is selectively expressed on Th2-type Tcells and has been shown to be responsible for Th2-dominant immuneresponses. In this study, we analyzed the expression of CCR4 in activesystemic lupus erythematosus (SLE) patients by FACS analysis usinganti-human CCR4 monoclonal antibody and determined the clinicalrelevance in this disease. Higher expression of CCR4 was found onperipheral blood CD4+ T lymphocytes of active SLE patients than wasfound with healthy controls and inactive SLE patients. The CCR4expression significantly correlated with the SLE disease activity index(SLEDAI) scores. The expression was dramatically decreased after thecorticosteroid therapy in parallel with a serum level ofdouble-stranded DNA antibody and SLEDAI scores. Moreover, we found thatserum levels of IL-10 were increased in active SLE patients andsignificantly correlated with the CCR4 expression. This study suggeststhat Th2 immune response is predominant in the active state of SLE, andCCR4 may have relevance in regard to the disease course in SLEpatients.
BCL-2 family expression in human neutrophils during delayed and accelerated apoptosis
Authors: Moulding Dale A , Akgul Cahit , Derouet Mathieu , White Michael R H , Edwards Steven W 
Published: September 2022

AbstractThe human neutrophil spontaneously undergoes apoptosis, but this type of cell death can be delayed or accelerated by a wide variety of agents. There are wide discrepancies in the literature regarding the expression of the Bcl-2 family of proteins in human neutrophils. Here, we show that A1, Mcl-1, Bcl-XL, and Bad are major transcripts in human neutrophils and that levels of these transcripts are cytokine regulated. However, no Bcl-XL protein was detected in Western blots. Protein levels for the proapoptotic proteins Bad, Bax, Bak, and Bik remained constant during culture, despite changes in the levels of mRNA for these gene products. These proapoptotic proteins were extremely stable, having very long half-lives. In contrast, A1 and Mcl-1 transcripts were extremely unstable (with ∼3-h half-lives), and Mcl-1 protein was also subject to rapid turnover. These results indicate that neutrophil survival is regulated by the inducible expression of the short-lived Mcl-1 and possibly the A1 gene products. In the absence of their continued expression, these prosurvival gene products are rapidly turned over, and then the activity of the stable death proteins predominates and promotes apoptosis.
Toll-like receptor 4-mediated activation of murine mast cells
Authors: McCurdy J D , Lin T-J , Marshall Jean S 
Published: September 2022

AbstractToll-like receptors (TLRs) are a family of pattern recognition receptors that are critical for cellular responses to a variety of bacterial, viral, and fungal products. Mast cells are important to host survival in a number of models of bacterial infection and might act as sentinel cells in host defense. We therefore examined the expression of TLRs and associated molecules by murine bone marrow-derived mast cells (BMMCs). BMMCs and the murine mast cell line MC/9 expressed mRNA for TLR2, TLR4, and TLR6 but not TLR5 and for both adapter molecule MD-2 and signaling molecule MyD88 but lacked surface CD14. After activation with the TLR2- and TLR4-dependent stimuli Staphylococcus aureus-derived peptidoglycan and Escherichia coli-derived lipopolysaccharide (LPS), respectively, mast cells produced significant levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). To determine whether mast cells require TLR4 for cellular responses to LPS, mast cells were derived from the bone marrow cells of C3H/HeJ and C57Bl/10ScNCr mice containing a point mutation and a null mutation, respectively, in TLR4. Using these models, we demonstrated that the BMMC IL-6 and TNF-α responses to LPS were completely dependent on functional TLR4 with no significant LPS response observed in its absence. These findings have important implications for the mechanism of mast cell responses to pathogens and their products and suggest that different TLR4-expressing cells might have different thresholds for activation with LPS.
Themicrophthalmiatranscription factor and the related helix-loop-helix zipper factors TFE-3 and TFE-C collaborate to activate the tartrate-resistant acid phosphatase promoter
Authors: Mansky Kim C , Sulzbacher Sabine , Purdom Georgia , Nelsen Lori , Hume David A , Rehli Michael , Ostrowski Michael C 
Published: September 2022

AbstractThe microphthalmia transcription factor (MITF) regulates different target genes in several distinct cell types, including osteoclasts. The role of the closely related factors TFE3 and TFEC in MITF action was studied. The TFE3 and TFEC proteins were expressed in osteoclast-like cells, and both could be immunoprecipitated in a complex with MITF. In transient transfection assays, TFE3 and TFEC could collaborate with MITF to superactivate the tartrate resistant acid phosphatase (TRAP) promoter, a target for MITF in osteoclasts. Although TFEC had been thought to act as a repressor, we could demonstrate that TFEC acted as a transactivator when fused to the gal4 DNA-binding domain in a yeast one-hybrid-type assay. Additionally, two mRNA isoforms of MITF, MITF-M and MITF-A, were detected in primary osteoclast-like cells by RT-PCR. In transient transfection assays, the MITF-A and MITF-M isoforms activated the promoter of the TRAP gene to the same extent, and both forms could collaborate equally well with TFE3 to activate the TRAP promoter. These results indicate that although different isoforms of MITF appear to be functionally similar, the TFE3 and TFEC proteins may collaborate with MITF to efficiently regulate expression of target genes in osteoclasts.
Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages
Authors: Raes Geert , De Baetselier Patrick , Noël Wim , Beschin Alain , Brombacher Frank , Hassanzadeh Gh. Gholamreza 
Published: September 2022

AbstractAlternatively activated macrophages (aaMφ) display molecular and biological characteristics that differ from those of classically activated macrophages (caMφ). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMφ, whereas in the late and chronic stages of infection, aaMφ develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMφ versus caMφ elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMφ as compared with caMφ. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-γ antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMφ and establish FIZZ1 and Ym1 as markers for aaMφ.
Physiological levels of 1α, 25 dihydroxyvitamin D3 induce the monocytic commitment of CD34+ hematopoietic progenitors
Authors: Grande Alexis , Montanari Monica , Tagliafico Enrico , Manfredini Rossella , Marani Tommaso Zanocco , Siena Michela , Tenedini Elena , Gallinelli Andrea , Ferrari Sergio 
Published: September 2022

AbstractAlthough supraphysiological levels of 1α, 25 dihydroxyvitamin D3 (VD) have been demonstrated extensively to induce the monomacrophagic differentiation of leukemic myelo- and monoblasts, little is known about the role that physiological levels of this vitamin could play in the regulation of normal hematopoiesis. To clarify this issue, we adopted a liquid-culture model in which cord blood CD34+ hematopoietic progenitors, induced to differentiate in the presence of different combinations of cytokines, were exposed to VD at various concentrations and stimulation modalities. The data obtained show that physiological levels of VD promote a differentiation of CD34+ hematopoietic progenitors characterized by the induction of all the monomacrophagic immunophenotypic and morphological markers. This effect is not only exerted at the terminal maturation but also at the commitment level, as demonstrated by the decrease of highly undifferentiated CD34+CD38− hematopoietic stem cells, the down-regulation of CD34 antigen, and the increase of monocyte-committed progenitors. Molecular analysis suggests that the VD genomic signaling pathway underlies the described differentiation effects.
Nitric oxide activates ATP-dependent K+ channels in human eosinophils
Authors: Schwingshackl Andreas , Moqbel Redwan , Duszyk Marek 
Published: September 2022

AbstractNitric oxide (NO) affects the function of ion channels in many cell types, but its role in the regulation of eosinophil ion channels is unknown. In this study, we used the perforated patch-clamp method to investigate the effect of endogenous and exogenous NO on eosinophil ion channels. Using the NO synthase inhibitor, N-nitro-l-arginine methyl ester, we showed that endogenous NO did not affect the whole-cell current in eosinophil. However, two NO donors, S-nitroso-glutathione and S-nitroso-N-acetyl penicillamine, activated whole-cell currents via a NO/cGMP-dependent pathway. Ion substitution and pharmacological studies showed that NO-activated currents were carried by K+ ions, likely through ATP-dependent K+ channels (KATP). Although RT-PCR studies showed the expression of several classes of K+ channels in human eosinophils, NO donors affected only KATP channel function. We conclude that NO, at concentrations likely to be encountered in vivo, could prevent eosinophil activation by opening KATP channels.