bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐12 production by human polymorphonuclear leukocytes
Authors: Cassatella Marco A. , Meda Lucia , Gasperini Sara , D'Andrea Annalisa , Ma Xiaojing , Trinchieri Giorgio 
Published: March 2007

AbstractHuman polymorphonuclear leukocytes (PMN) stimulated by lipopolysaccharide (LPS) produce interleukin‐12 (IL‐12). Both the free IL‐12 p40 chain and minute amounts of the biologically active IL‐12 p70 heterodimers are produced by PMN. Interferon‐γ (IFN‐γ) enhanced the LPS‐induced secretion of both the free IL‐12 p40 chain and the p70 heterodimer by approximately fivefold. As observed for other IL‐12‐producing cell types, the ratio of free p40 chain to p70 heterodimer secreted by LPS‐stimulated PMN was approximately 20:1. LPS induced a 100‐fold increase of IL‐12 p40 mRNA, but had minimal effect on p35 mRNA accumulation, IFN‐γ enhanced the LPS‐induced accumulation of p40 mRNA and directly induced a several‐fold increase in the accumulation of p35 mRNA. Therefore, the combined effect of LPS and IFN‐γ induced sufficient expression of both p40 and p35 to attain production of the biologically active p70 heterodimer at physiologically relevant concentrations. The ratio between p40 and p35 mRNA abundance in PMN stimulated with both LPS and IFN‐γ was approximately 200:1, explaining the secretion of the free p40 chain in much higher concentrations than the p70 heterodimer. IL‐10, an inhibitor of the production of various cytokines in PMN, also suppressed IL‐12 mRNA accumulation and secretion by PMN. Because of the important immunoregulatory function of IL‐12, in particular induction of IFN‐γ production and facilitation of T helper cell type 1 response, the ability of PMN to produce IL‐12 suggests that neutrophils may play an active role in the regulatory interaction between innate resistance and adaptive immunity.
Anti‐acetylcholinesterase antibodies display cholinesterase‐like activity
Authors: Johnson Glynis , Moore Samuel W. 
Published: March 2007

AbstractA monoclonal antibody (mAb) raised against human acetylcholinesterase (AChE) was found to have catalytic activity. A similar phenomenon was observed in a polyclonal antibody raised against the same antigen. The antibodies were demonstrated to be pure, and no contamination with either AChE or butyryl‐cholinesterase was found. Both antibodies hydrolyzed acetylthiocholine, an AChE substrate, and the mAb followed Michaelis‐Menten kinetics. Six other mAb and one other polyclonal antibody showed no evidence of catalytic activity. This development of cholinesterase‐like behavior by certain anti‐AChE antibodies may have arisen by stable complexation of the enzyme with a substrate or inhibitor during antigen presentation. This phenomenon may have implications for the diagnostic measurement of AChE activity as well as in assessing the immunological reasons for the markedly raised AChE level in developmental conditions such as Hirschsprung's disease.
Poor loading of major histocompatibility complex class II molecules with endogenously synthesized short peptides in the absence of invariant chain
Authors: Busch Robert , Vturina Iryna Y. , Drexler Johannes , Momburg Frank , Hämmerling Günter J. 
Published: March 2007

AbstractIn normal antigen‐presenting cells, newly synthesized major histocompatibility complex (MHC) class II molecules associate with the invariant chain (Ii) glycoprotein in the endoplasmic reticulum (ER). They are loaded with peptides only after proteolytic removal of the Ii in post‐Golgi endocytic vesicles. Since the Ii inhibits peptide binding to MHC class II molecules, this association could protect MHC class II molecules from being loaded with endogenous peptides early after biosynthesis. If this were an important function of the Ii in vivo, MHC class II molecules synthesized in cells lacking the Ii should be loaded efficiently with short endogenous peptides in the ER; such peptides are known to be present there due to TAP‐mediated import from the cytosol. To examine this possibility, we have studied peptide loading in HeLa transfectants expressing murine H‐2Ak MHC class II molecules either alone or together with an excess of Ii. Endogenous peptides could readily be extracted from conformationally intact Ak αβ dimers of biosynthetically labeled Ii+ cells, whereas peptide loading was greatly (> 95%) diminished in the absence of Ii. Significant amounts of sodium dodecyl sulfate‐(SDS) stable 55‐kDa peptide: Ak complexes were only found in the Ii+ transfectants. In the absence of Ii, the MHC class II molecules instead formed stable complexes with long (20 and 50 kDa) polypeptides. Known Ak‐binding peptides bound stably to Ak molecules on Ii− cells, could be co‐purified with them, and were resistant to release in SDS, suggesting that poor recovery of endogenous peptides was not due to decreased stability of Ak: peptide complexes in the absence of Ii. We conclude that protection of MHC class II molecules from endogenous short peptides does not appear to be a quantitatively important function of the Ii molecule, because peptide loading is inefficient in its absence.
Differential modulation of T helper type 1 (Th1) and T helper type 2 (Th2) cytokine secretion by prostaglandin E2 critically depends on interleukin‐2
Authors: Hilkens Catharien M. U. , Vermeulen Hans , van Neerven R. J. Joost , Snijdewint Frank G. M. , Wierenga Eddy A. , Kapsenber Martien L. 
Published: March 2007

AbstractProstaglandin E2 (PGE2) favors T helper type 2 (Th2)‐like cytokine secretion profiles in murine and human CD4+ T cells by inhibiting the production of the Th1‐associated cytokines interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) and up‐regulating the production of the Th2‐associated cytokines IL‐4 and IL‐5 in a dose‐dependent way. However, the potent inhibition of IL‐2 production by PGE2 seems to be in contrast with the simultaneous up‐regulation of IL‐4 and IL‐5 production, because the induction of these cytokines requires IL‐2. We, therefore, investigated to which extent the net modulatory effect of PGE2 is determined by the availability of IL‐2. To this aim, we examined the effects of PGE2 on the cytokine secretion profiles of a panel of human Th0 clones upon stimulation via different activation pathways, resulting either in high or low IL‐2 production. The differential modulation of Th1 and Th2 cytokines by PGE2 was observed only upon modes of stimulation resulting in high IL‐2 production. When IL‐2 production was low, PGE2 inhibited the secretion of all four cytokines. These different modulation patterns were directly related to the IL‐2 availability, because (i) neutralizing antibody to IL‐2 abrogated the up‐regulatory effect of PGE2 on IL‐4 and IL‐5 secretion in experiments with high endogenous IL‐2 levels, (ii) lack of differential cytokine modulation by PGE2 in conditions with low levels of endogenous IL‐2 could be restored with exogenous IL‐2, and (iii) cell viability was comparable in all conditions. These results demonstrate that the net modulatory effect of PGE2 on the cytokine secretion profile of T cells critically depends on the availability of IL‐2. Since this parameter varies with the experimental conditions and the T cell population studied, this finding may explain why certain immune responses may be either up‐ or down‐regulated by PGE2 under different conditions.
Cross‐reactive trinitrophenylated peptides as antigens for class II major histocompatibility complex‐restricted T cells and inducers of contact sensitivity in mice. Limited T cell receptor repertoire
Authors: Kohler Jochen , Martin Stefan , Pflugfelder Ulrike , Ruh Helga , Vollmer Jörg , Weltzien Hans Ulrich 
Published: March 2007

AbstractThe induction of contact sensitivity in mice by hapten reagents such as trinitrochlorobenzene (TNCB) involves the activation of class II major histocompatibility complex (MHC)‐restricted, hapten‐specific, CD4+ T cells. Reports from different laboratories have indicated that the relevant antigenic epitopes in such reactions might include hapten‐conjugated, MHC class II‐associated peptides. This study for the first time directly demonstrates that hapten‐peptides account for the majority of determinants recognized by trinitrophenyl (TNP)‐specific CD4+ T lymphocytes. The sequences of those TNP carrier peptides do not have to be related to mouse proteins. Thus, we show that TNP‐modified peptides derived from mouse IgG, pigeon cytochrome c or staphylococcal nuclease known to bind to I‐Ab or from λ represser with specificity to I‐Ad as well as TNP‐proteins such as bovine serum albumin, ovalbumin or keyhole limpet hemocyanin all create class II‐restricted hapten determinants for a number of TNP‐specific T cell clones and hybridomas. All of these cells were induced with cells modified by trinitrobenzene sulfonic acid (TNBS). In addition, we present arguments indicating that individual TNP‐specific helper T cells may cross‐react with different TNP‐peptides bound to identical class II molecules. Chemical treatment of antigen‐presenting cells with TNCB or TNBS may thus result in a limited number of particularly repetitive immunodominant hapten epitopes. Immunodominant epitopes were also indicated by an overrepresentation of the TCR elements Vβ2 and Vα10 in I‐Ab/TNP‐specific T cells. Most importantly, however, we demonstrate that TNP attached to lysine 97 in the staphylococcal nuclease peptide 93–105 (i.e. a clearly “non‐self” sequence) is able to prime mice for subsequent elicitation of contact sensitivity by TNCB in the absence of foreign protein. We take this to indicate that those TNP‐peptide determinants defined by us as immuno‐dominant are responsible for the induction of contact sensitivity to haptens.
Enhanced tumor necrosis factor suppression and cyclic adenosine monophosphate accumulation by combination of phosphodiesterase inhibitors and prostanoids
Authors: Sinha Bhanu , Semmler Jan , Eisenhut Tobias , Eigler Andreas , Endres Stefan 
Published: March 2007

AbstractWe investigated cooperative effects of phosphodiesterase (PDE) inhibitors and prostanoids on cyclic adenosine monophosphate (cAMP) accumulation and tumor necrosis factor (TNF)‐α synthesis in human peripheral blood mononuclear cells (PBMC). PDE inhibitors alone induced only a small increase in cAMP levels in lipopolysaccharide (LPS)‐stimulated PBMC. Cicaprost (a stable analogue of prostacyclin) and pentoxifylline added simultaneously to LPS‐stimulated PBMC (2.0 × 106/ml) induced a rapid increase of cAMP to a level of 100 nM that peaked within 10 min and remained at a plateau for up to 4 h. Thus combined prostanoids and PDE inhibitors enhanced cAMP accumulation. TNF‐α suppression in the presence of pentoxifylline and prostanoids exceeded that of either drug alone. The potency of different PDE inhibitors (theophylline, pentoxifylline, penthy‐droxifylline, albifylline, torbafylline, A 802715, amrinone and rolipram) to increase cAMP levels in combination with cicaprost was evaluated after 1 h of incubation. The dose‐dependent increase of cAMP for all PDE inhibitors tested in this combined stimulation provided a useful tool for evaluating the potency of PDE inhibitors on cAMP accumulation. The effective concentration of PDE inhibitors, which raised cAMP levels to 300% of control, (EC300), correlated with the IC50 for TNF‐α suppression (r = 0.930, p = 0.007, with theophylline excluded from the analysis). Interestingly, by contrast, the specific type IV PDE inhibitor rolipram caused only a moderate rise of accumulated cAMP in the same cells. Our data support cAMP as an essential mediator for TNF‐α suppression by PDE inhibitors. Furthermore, an enhanced inhibiting effect on TNF‐α production may prove therapeutically advantageous. It may occur in inflammatory and infectious diseases in vivo, since high levels of endogenous prostaglandins are liberated in these conditions.
Selective enhancing effect of the Yaa gene on immune responses against self and foreign antigens
Authors: Fossati Liliane , Iwamoto Masahiro , Merino Ramón , Izui Shozo 
Published: March 2007

AbstractThe BXSB Y chromosome‐linked mutant gene, Yaa, accelerates the progression of a lupus‐like autoimmune syndrome only in mice that are predisposed to autoimmune diseases. Unlike the lpr gene, which causes the defects in the Fas antigen‐mediating apoptosis, the autoimmune enhancing activity of the Yaa gene is selective, depending on autoantigens, and varies among lupus‐prone mice. To obtain a better definition of the role of the Yaa gene in the acceleration of autoimmune disease, we have investigated immune responses to several foreign antigens to determine whether the Yaa gene is able to potentiate immune responses to foreign antigens in a selective manner. We report here that the Yaa gene potentiated immune responses against foreign antigens only in mice which are genetically (H‐2‐linked) low responding, but not high or non‐responding. Moreover, studies on Yaa+‐Yaa− double bone marrow chimeric mice revealed that B cells from Yaa+ mice were selectively stimulated to produce antibodies to low‐responding antigen, human IgG, while both B cell populations similarly responded to high‐responding antigen, ovalbumin. Our results suggest that first, the selective immune enhancing activity of the Yaa gene may be related to differences in the capacity of T helper cells specific for given self or foreign antigens; and second, a specific cognate interaction of T helper cells with Yaa+ B cells is apparently responsible for the selective enhancement of immune responses to antigens, to which mice are genetically low responding.
Recombinant CD4‐IgE, a novel hybrid molecule, inducing basophils to respond to human immunodeficiency virus (HIV) and HIV‐infected target cells
Authors: Krauss Susanne , Kufer Peter , Federle Christine , Tabaszewski Pjotr , Weiss Elisabeth , Rieber E. Peter , Riethmüller Gert 
Published: March 2007

AbstractBasophils and mast cells, as the main effector cells in IgE‐mediated type I hypersensitivity, are involved in the elimination of parasites and, according to recent findings, may also play an important role in the defense against bacterial and viral infections. Using a genetic engineering approach we wanted to redirect this potent IgE‐mediated defense system against intruding human immune deficiency virus. We constructed a recombinant CD4‐IgE molecule, consisting of the two N‐terminal domains of CD4 and the CH2–4 domains of the IgE heavy chain, thus providing the IgE with specificity for the gp120 of human immunodeficiency virus (HIV). The binding properties of hybrid CD4‐IgE to the high‐affinity receptor for IgE (FcεRI) on basophils as well as to the low‐affinity receptor (FcεRII or CD23) for IgE on lymphoid cells were found to be similar to those of native IgE. At the same time, the CD4 domains of the recombinant molecule retained the gp120 binding specificity with an affinity similar to that of the native CD4. By functional tests, we demonstrated that CD4‐IgE armed basophils can be triggered by free HIV and by HIV‐infected cells to release their mediators. We further show that HIV‐triggered basophils lead to a decreased replication of HIV in susceptible T cells. We, therefore, conclude that the type I hypersensitivity effector cells can be engaged in the elimination of HIV‐infected cells, at least in vitro. Because of the strong binding of the CD4‐IgE construct to the FcεRI, we assume that CD4‐IgE has a short t1/2 in serum, but may similarly to IgE exhibit prolonged resident time on basophils and mast cells, which are located close to mucosal surfaces or in the connective tissue. Thus CD4‐IgE could play an important role in the elimination of HIV also in vivo.
Mouse interleukin‐12 (IL‐12) p40 homodimer: a potent IL‐12 antagonist
Authors: Gillessen Silke , Carvajal Daisy , Ling Ping , Podlaski Frank J. , Stremlo Donna L. , Familletti Philip C. , Gubler Ueli , Presky David H. , Stern Alvin S. , Gately Maurice K. 
Published: March 2007

AbstractInterleukin‐12 (IL‐12) is a cytokine that has regulatory effects on T and natural killer (NK) cells and is composed of two disulfide‐bonded subunits, p40 and p35. It was recently reported that supernatants from cultures of mouse IL‐12 (moIL‐12) p40‐transfected COS cells could inhibit IL‐12‐dependent responses in vitro (Mattner, F., et al., Eur. J. Immunol. 1993. 23: 2202). We have further characterized the nature of the inhibitory substance. Purified mouse p40 produced in a baculovirus expression system was found to consist of two species: the p40 monomer and a disulfide‐linked p40 dimer [(p40)2]. The (p40)2 was 25‐ to 50‐fold more active than the p40 monomer in causing specific, dose‐dependent inhibition of IL‐12‐induced mouse concanavalin A (Con A) blast proliferation and could also inhibit IL‐12‐induced interferon‐λ (IFN‐λ) secretion by mouse splenocytes and IL‐12‐dependent activation of mouse NK cells. Competitive binding studies on mouse Con A blasts showed that (p40)2 was equally effective as moIL‐12 in competing with 125I‐labeled moIL‐12 ([125I]moIL‐12) for binding to mouse Con A blasts. However, in contrast to moIL‐12, mouse (p40)2 displayed little ability to compete with 125I‐labeled human IL‐12 (huIL‐12) for binding to high‐affinity IL‐12 receptors (IL‐12R) on human phytohemagglutinin (PHA) blasts and caused little or no inhibition of huIL‐12‐induced human PHA blast proliferation. Nonetheless, mouse (p40)2 was equally effective as moIL‐12 in competing with [125I] huIL‐12 for binding to COS cells transfected with the human IL‐12R β subunit and expressing low‐affinity IL‐12 binding sites. These results suggest that (i) the majority of the structural determinants required for binding of IL‐12 to its receptor are contained within the p40 subunit, but p35 is required for signaling, (ii) the p40 subunit of IL‐12 interacts with the β subunit of IL‐12R, and (iii) (p40)2 may be a suitable IL‐12 antagonist for studying the role of IL‐12 in various immune responses in vivo as well as in vitro. Further studies are required to determine whether or not (p40)2 is produced by normal lymphoid cells and is a physiologic regulator of IL‐12 activity.
Macrophage inflammatory protein‐1α influences eosinophil recruitment in antigen‐specific airway inflammation
Authors: Lukacs Nicholas W. , Strieter Robert M. , Shaklee Christine L. , Chensue Stephen W. , Kunkel Steven L. 
Published: March 2007

AbstractAllergic airway inflammation is characterized by peribronchial eosinophil accumulation within the submucosa of the airway of the lung. In the present study we have utilized a model of airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg antigen (SEA) in presensitized mice. The recruitment of neutrophils and eosinophils into the airway was found to be maximal at 8 and 48 h post challenge, respectively. Since macrophage inflammatory protein‐1α (MIP‐1α) has previously been found to be chemotactic for eosinophils, in vitro, we postulated that MIP‐1α was involved in the airway inflammation and more specifically in eosinophil recruitment into the airway. Initial studies demonstrated an increase in MIP‐1α mRNA expression at 8 h post‐SEA challenge, as compared to vehicle‐treated control mice. We next demonstrated a significant increase in MIP‐1α protein in the lungs of SEA‐challenged mice at 8 h compared to control challenged mice, correlating to the mRNA data. Immunohistochemical staining of lungs from SEA‐challenged mice demonstrated MIP‐1α protein expression in airway epithelial cells, alveolar macrophages and in recruited mononuclear cell populations. Immunolocalization of MIP‐1α to cells within the bronchoalveolar lavage fluid demonstrated that macrophages and eosinophils stained positive for the protein. To determine the contribution of MIP‐1α expression to eosinophil accumulation, SEA‐challenged mice were passively immunized with either neutralizing MIP‐1α antibodies or normal rabbit IgG, 3–4 h prior to the intratracheal SEA challenge. These studies demonstrated a > 50% decrease in eosinophil recruitment to the lungs and airway in animals receiving neutralizing MIP‐1α antibodies with no effect on early neutrophil recruitment. These results suggest that the production of MIP‐1α, induced by an antigen‐specific response, plays an important role in recruitment of eosinophils in this airway model of inflammation.
Immunoglobulin heavy chain germ‐line JH−Cμ transcription in human precursor B lymphocytes initiates in a unique region upstream of DQ52
Authors: Thompson Allan , Timmers Erik , Schuurman Ruud K. B. , Hendriks Rudolf W. 
Published: March 2007

AbstractFrom human precursor B cells which had both immunoglobulin (Ig) heavy (H) chain loci in germ‐line configuration, various IgH chain germ‐line transcripts were isolated and sequenced. These transcripts were shown to contain sequences derived from the JH region, the IgH chain enhancer element or the Ig switch region. A number of isolated cDNA clones contained sequences at their 5′ end that were derived from a single exon located just upstream of DQ52, designated the μ° element. Sequence analysis of a 920‐bp genomic DNA segment, containing the μ° exon and its 5′ flanking region, revealed the presence of various conserved motifs for DNA‐binding proteins, such as E2A, Ets, NF‐χB and AP‐2, which have previously been found in the IgH and L chain enhancers. We propose that the activity of μ° element, resulting in germ‐line transcription of the DQ52‐JH gene segment, is required to generate full accessibility for the V(D)J recombinase.
Lymphocytic CD43 and CD45 bear sulfate residues potentially implicated in cell to cell interactions
Authors: Giordanengo Valérie , Limouse Martine , Peyron Jean‐François , Lefebvre Jean‐Claude 
Published: March 2007

AbstractCD43 is a major heavily glycosylated lymphocyte surface molecule. It has been shown to play an important role in lymphocyte activation and cell‐cell interactions. Here we demonstrate that in human activated lymphocytes and CEM T cells, CD43 is a sulfated molecule. We also observed that CD45, another lymphocyte surface glycoprotein, is a sulfated molecule. 35SO incorporation would thus appear to be an appropriate labeling method for CD43 and CD45 visualization. Moreover, we show that the level of cell surface protein sulfation can modulate CD43‐mediated homotypic aggregation induced by CD43 monoclonal antibodies. It is well known that glycoprotein sulfation is required for various recognition phenomena. Since there are numerous potential sulfation sites on CD43 and CD45, these residues could play an important role in regulating cell‐cell interactions.