bluuebunny/crossref_metadata_2025_split huggingface dataset:
MIP-1α regulates CD4+ T cell chemotaxis and indirectly enhances PMN persistence inPseudomonas aeruginosacorneal infection
Authors: Kernacki Karen A , Barrett Ronald P , McClellan Sharon , Hazlett Linda D 
Published: September 2022

AbstractThe role of macrophage inflammatory protein-1α (MIP-1α) in cell infiltration into Pseudomonas aeruginosa-infected cornea and subsequent disease was examined. Greater amounts of the chemokine (protein and mRNA) were found in the infected cornea of susceptible B6 (“cornea perforates”) versus resistant BALB/c (“cornea heals”) mice from 1 to 5 days postinfection. Treatment of BALB/c mice with recombinant (r) MIP-1α exacerbated disease and was associated with an increased number of neutrophils (PMNs) in the cornea. Treatment of BALB/c mice with rMIP-1α also induced recruitment of activated CD4+ T cells into the affected cornea, converting resistant to susceptible mice. Depleting CD4+ T cells in r-treated BALB/c mice significantly decreased PMNs in cornea tissue, suggesting that T cells regulate persistence of PMNs at this site. In B6 mice, administration of neutralizing MIP-1α polyclonal antibody also significantly reduced PMN numbers and pathology. Collectively, evidence is provided that MIP-1α directly contributed to CD4+ T cell recruitment and indirectly to PMN persistence in the infected cornea.
IL-17: prototype member of an emerging cytokine family
Authors: Aggarwal Sudeepta , Gurney Austin L 
Published: September 2022

AbstractIL-17 is a potent proinflammatory cytokine produced by activated memory T cells. The large-scale sequencing of the human and other vertebrate genomes has revealed the presence of additional genes encoding proteins clearly related to IL-17, thus defining a new family of cytokines. There are at least six members of the IL-17 family in humans and in mice. Initial characterization suggests that like IL-17, several of these newly identified molecules have the ability to modulate immune function. Neither the IL-17 family nor the cognate receptors that have been identified for these molecules bear obvious sequence similarity to other known families of proteins. Thus, they represent a distinct signaling system that appears to have been highly conserved across vertebrate evolution. The potent inflammatory actions that have been identified for several of these factors and the emerging associations with major human diseases suggest that these proteins may have significant roles in inflammatory processes.
NK-like CD8+ cells in immunologically naïve neonatal calves that respond to dendritic cells infected withMycobacterium bovisBCG
Authors: Hope Jayne C , Sopp Paul , Howard Chris J 
Published: September 2022

AbstractPre-exposure to environmental mycobacteria and induction of an inappropriately biased immune response may be major factors affecting the efficacy of BCG; vaccination of neonates that have not been exposed to environmental mycobacteria may induce more effective immunity. Responses of neonatal calves to mycobacterial antigens using dendritic cells (DC) as antigen-presenting cells were investigated. In nonvaccinated, immunologically naive calves as young as 1 day old, a population of CD8+ cells proliferated and produced IFN-γ in response to BCG-infected DC. CD3− CD8+ NK-like and CD3+ CD8+ T cells were evident within the responding CD8+ population. The response was not MHC-restricted. The NK-like CD3− cells were the major population producing IFN-γ. The presence of mycobacteria-reactive, IFN-γ-secreting CD8+ NK cells in neonatal calves may have important consequences for the induction of a Th1-biased immune response.
The role of growth hormone in T-cell development and reconstitution
Authors: Welniak Lisbeth A , Sun Rui , Murphy William J 
Published: September 2022

AbstractGrowth hormone (GH), directly or through GH-induction of insulin-like growth factor (IGF)-1, has been implicated in lymphocyte development and function. Recent studies have questioned the role of GH and IGF-1 in immune responses. This review examines experimental data describing the immunoregulatory function of GH and attempts to reconcile the literature.
Enhanced proinflammatory response to endotoxin after priming of macrophages with lead ions
Authors: Flohé Stefanie B , Brüggemann Jutta , Herder Christian , Goebel Carsten , Kolb Hubert 
Published: September 2022

AbstractExposure to lead ions strongly enhances the susceptibility of rodents to endotoxin shock and parasitical infections. Macrophages play a key role during the immune response to lipopolysaccharide (LPS) and during the defense against parasites and might be a target of lead. In the present study, bone marrow-derived macrophages (BMMφ) pretreated with lead chloride prior to stimulation with LPS were analyzed for their release of immune mediators. Lead-pretreated cells released up to tenfold increased amounts of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-12, and prostaglandin E2 (PGE2) but less IL-10 compared with controls. These effects were paralleled by enhanced mRNA levels and were dependent on the duration of lead pretreatment. Inhibition of protein kinase C or of protein synthesis during the priming phase blocked the lead-induced increase of TNF-α and IL-6 release. In conclusion, lead ions prime ΒMMφ for enhanced proinflammatory cytokine secretion in response to LPS, likely by activation of protein kinase C and subsequent synthesis of an unidentified mediator.
RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs)
Authors: Collison Kate S , Parhar Ranjit S , Saleh Soad S , Meyer Brian F , Kwaasi Aaron A , Hammami Muhammad M , Schmidt Ann Marie , Stern David M , Al-Mohanna Futwan A 
Published: September 2022

AbstractThe accumulation of advanced glycation end products (AGEs) in the tissue and serum of subjects with diabetes has been linked to the pathogenesis of vascular complications. Because diabetes may be also complicated by increased susceptibility to recurrent infection, we investigated the effects of AGEs on human neutrophils, because their burst of activity immediately upon engagement of pathogens or other inflammatory triggers is critical to host response. We demonstrate the presence of receptor for advanced glycation end products (RAGE) at the message and protein levels. We also demonstrate that AGE albumin (but not control albumin) binds with high affinity to human neutrophils (Kd of 3.7±0.4 nM). The binding was blocked almost completely by excess soluble RAGE, anti-RAGE antibodies, or antibodies to CML-modified albumin. AGE albumin induced a dose-dependent increase in intracellular-free calcium as well as actin polymerization. Further, AGE albumin inhibited transendothelial migration and Staphylococcus aureus-induced but not fMLP-induced production of reactive oxygen metabolite. Moreover, although AGE albumin enhanced neutrophil phagocytosis of S. aureus, it inhibited bacterial killing. We conclude that functional RAGE is present on the plasma membrane of human neutrophils and is linked to Ca2+ and actin polymerization, and engagement of RAGE impairs neutrophil functions.
Engagement of α4β1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine
Authors: de la Fuente Mª Teresa , Casanova Benito , Moyano José V , Garcia-Gila Mercedes , Sanz Laura , Garcia-Marco José , Silva Augusto , Garcia-Pardo Angeles 
Published: September 2022

AbstractB-cell chronic lymphocytic leukemia is characterized by the accumulation of malignant B lymphocytes as a result of abnormal survival signals operating in vivo. Previously, we showed that adhesion of B-CLL cells to the fibronectin fragment H89, a ligand for α4β1 integrin, prevents their spontaneous apoptosis in vitro. We have now studied whether α4β1/H89 interaction affected the response of B-CLL cells to the therapeutic drug fludarabine. B-CLL cells cultured on H89 during treatment with fludarabine showed significantly higher mean viability (P&lt;0.05) than cells cultured on the control polylysine for all doses of drug tested. Similar results were obtained with the EHEB cell line. Analysis of the expression of Bcl-2-family proteins after 48 h of fludarabine treatment revealed that Bcl-xL levels were significantly higher (P&lt;0.05) for cells cultured on H89 than on polylysine and correlated (r=0.56,P&lt;0.05) with the increased cell viability observed on H89 cultures. These results indicate that Bcl-xL is involved in the survival signals induced by α4β1 ligation and may contribute to the progressive drug resistance observed in B-CLL.
Differentiation of human basophils: an overview of recent advances and pending questions
Authors: Arock Michel , Schneider Elke , Boissan Mathieu , Tricottet Viviane , Dy Michel 
Published: September 2022

AbstractBasophils are rare, circulating leukocytes derived from hematopoietic CD34+ progenitors. The identification of cytokines promoting their development in vitro has led to substantial advances in understanding their differentiation process. An important role could be assigned to interleukin-3 (IL-3), which supports the maturation of hematopoietic progenitors into basophils in vitro and in vivo. In contrast to other myeloid lineages, a specific basophil growth factor has not yet been discovered. Furthermore, it is still unclear whether basophils possess a lineage-restricted progenitor or whether they share a common ancestor with mast cells (MC), eosinophils, or even megakaryocytes. Partial answers to these questions could be provided using in vitro culture systems or taking advantage of hematological disorders, such as chronic and acute myeloid leukemia (CML and AML), some myelodysplastic syndromes, and the very rare acute basophilic leukemia in which basophilic differentiation occurs.
Interferon-α as an immunotherapeutic protein
Authors: Brassard Diana L , Grace Michael J , Bordens Ronald W 
Published: September 2022

AbstractInterferon-α (IFN-α) has proven to be a clinically effective antiviral and antineoplastic therapeutic drug for more than 16 years. During this time, evidence from in vitro laboratory studies and the clinical arena has supported the concept that IFN-α is an immunotherapeutic drug. By regulating a diverse set of cytokines and their receptors, IFN-α is uniquely positioned to prime the host immune response and provide an effective antineoplastic- and antiviral-immune response. IFN-α stimulates the innate cell-mediated response and then participates in the transition of the initial host innate response into an effective adaptive-immune response. IFN-α also drives the adaptive cell-mediated CD8+ T-cell response and helps to maintain a CD4+ Th1-cell population balance for an effective antineoplastic and antiviral host defense. This review will describe the current state of knowledge of IFN-α as an immunoregulatory protein and address specific issues of IFN-α as an immunotherapeutic for antineoplastic and antiviral diseases.
Erythrocytes deliver Tat to interferon-γ-treated human dendritic cells for efficient initiation of specific type 1 immune responses in vitro
Authors: Corinti Silvia , Chiarantini Laura , Dominici Sabrina , Laguardia Maria Elena , Magnani Mauro , Girolomoni Giampiero 
Published: September 2022

AbstractDendritic cells (DC) can represent an important target for vaccine development against viral infections. Here, we studied whether interferon-γ (IFN-γ) could improve the functions of DC and analyzed human red blood cells (RBC) as a delivery system for Tat protein. Monocyte-derived DC were cultured in human serum and matured with monocyte-conditioned medium (MCM) in the presence or not of IFN-γ. Tat was conjugated to RBC (RBC-Tat) through avidin-biotin bridges. Stimulation of DC with IFN-γ increased the release of interleukin (IL)-12 and tumor necrosis factor-α and inhibited the production of IL-10. Moreover, IFN-γ-treated DC up-regulated the release of CXCL10 (IP-10) markedly and reduced the secretion of CCL17 TARC significantly, attracting preferentially T-helper (Th)1 and Th2 cells, respectively. DC internalized RBC-Tat efficiently. Compared with DC pulsed with soluble Tat, DC incubated with RBC-Tat elicited specific CD4+ and CD8+ T-cell responses at a much lower antigen dose. DC matured in the presence of MCM were more effective than immature DC in inducing T-cell proliferation and IFN-γ release. Finally, immature and mature DC exposed to IFN-γ were better stimulators of allogeneic T cells and induced a higher IFN-γ production from Tat-specific CD4+ and CD8+ T lymphocytes. In conclusion, erythrocytes appear an effective tool for antigen delivery into DC, and IFN-γ could be used advantageously for augmenting the ability of DC to induce type 1 immune responses.
Transforming growth factor β signal transduction
Authors: Dennler Sylviane , Goumans Marie-José , ten Dijke Peter 
Published: September 2022

AbstractTransforming growth factor beta1 (TGF-β1) is the prototypic member of a large family of structurally related pleiotropic-secreted cytokines that play a pivotal role in the control of differentiation, proliferation, and state of activation of many different cell types including immune cells. TGF-β family members have potent immunosuppressor activities in vitro and in vivo. These cytokines trigger their biological effects by inducing the formation of a heteromeric transmembrane serine/threonine kinase receptor complex. These receptors then initiate intracellular signaling through activation of Smad proteins, and specific Smads become phosphorylated and associate with other Smads. These heteromeric Smad complexes accumulate in the nucleus, where they modulate the expression of target genes. Recent data support the notion that Smads are important intracellular effectors of TGF-β in immune cells. Here, we review recent advances in TGF-β signal transduction in immune cells.
Adhesion to extracellular matrix proteins modulates bovine neutrophil responses to inflammatory mediators
Authors: Borgquist Jessica D , Quinn Mark T , Swain Steve D 
Published: September 2022

AbstractThe neutrophil inflammatory response can be altered profoundly by contact with extracellular matrix proteins (ECMs). We characterized functional responses (intracellular calcium, actin polymerization, degranulation, adhesion, and oxidative burst) of bovine neutrophils adhered to selected ECM proteins [collagen IV, laminin, fibronectin, thrombospondin, and heparan sulfate proteoglycan (HSP)] in response to interleukin-8 (IL-8) and platelet-activating factor (PAF). Neutrophil adhesion to ECMs altered responses to PAF and IL-8, although some functions were more responsive to modulation. The most susceptible function was reactive oxygen species (ROS) production. ROS production in response to PMA and TNF-α was supported differentially by various ECMs, and PAF and IL-8 “priming” had strikingly different effects, depending on the ECM present. Although PAF and IL-8 inhibited TNF-α-induced ROS production in neutrophils adhered to collagen, fibronectin, and laminin, PAF enhanced ROS production strongly in HSP-adherent cells. This study illustrates how neutrophils can integrate multiple stimuli, resulting in complex modulation of their functional response.
The immunosuppressive effects of chronic morphine treatment are partially dependent on corticosterone and mediated by the μ-opioid receptor
Authors: Wang Jinghua , Charboneau Richard , Balasubramanian Sudha , Barke Roderick A , Loh Horace H , Roy Sabita 
Published: September 2022

AbstractWild-type and μ-opioid receptor knockout (MORKO) mice were used to investigate the role of corticosterone (CORT) and the μ-opioid receptor (MOR) in chronic morphine-mediated immunosuppression. We found that although plasma CORT concentrations in CORT infusion (10 mg/kg/day) and morphine-pellet implantation (75 mg) mice were similar (400–450 ng/ml), chronic morphine treatment resulted in a significantly higher (two- to threefold) inhibition of thymic, splenic, and lymph node cellularity; inhibition of thymic-lymphocyte proliferation; inhibition of IL-2 synthesis; and activation of macrophage nitric oxide (NO) production when compared with CORT infusion. In addition, results show that the inhibition of IFN-γ synthesis and splenic- and lymph node-lymphocyte proliferation and activation of macrophage TNF-α and IL-1β synthesis occurred only with chronic morphine treatment but not with CORT infusion. These morphine effects were abolished in MORKO mice. The role of the sympathetic nervous system on morphine-mediated effects was investigated by using the ganglionic blocker chlorisondamine. Our results show that chlorisondamine was able to only partially reverse morphine's inhibitory effects. The results clearly show that morphine-induced immunosuppression is mediated by the MOR and that although some functions are amplified in the presence of CORT or sympathetic activation, the inhibition of IFN-γ synthesis and activation of macrophage-cytokine synthesis is CORT-independent and only partially dependent on sympathetic activation.
Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide
Authors: Gürsel Mayda , Verthelyi Daniela , Gürsel Ihsan , Ishii Ken J , Klinman Dennis M 
Published: September 2022

AbstractSynthetic oligodeoxynucleotides (ODN) expressing “CpG motifs” show promise as immune adjuvants, antiallergens, anticancer, and immunoprotective agents. Two structurally distinct classes of CpG ODN have been identified that stimulate human PBMC. This work establishes that both types of ODN bind to and are internalized by the same individual B cells, NK cells, and monocytes. However, the intracellular localization of “D” and “K” ODN differs, as does their functional activity: “K” type ODN trigger monocytes and B cells to proliferate and secrete IL-6 and IgM, whereas “D” type ODN induce NK cells to produce IFN-γ and monocytes to differentiate into CD83+/CD86+ dendritic cells. In monocytes, these two types of ODN (which differ in backbone composition and CpG motif) cross-inhibit one another's activity. Thus, different types of CpG ODN have distinct and in some cases incompatible effects on the same cells, a finding with important implications for the therapeutic use of these agents.
Recognition and phagocytosis of apoptotic T cells by resident murine tissue macrophages require multiple signal transduction events
Authors: Hu Bin , Punturieri Antonello , Todt Jill , Sonstein Joanne , Polak Timothy , Curtis Jeffrey L 
Published: September 2022

AbstractMacrophages (Mø) ingest apoptotic cells with unique effects on their cytokine production, but the signaling pathways involved are virtually unknown. Signal transduction in response to recognition of apoptotic thymocytes by resident murine alveolar (AMø) or peritoneal (PMø) Mø was studied by in vitro phagocytosis assay. Phagocytosis was decreased in a dose-dependent and nontoxic manner by inhibiting phosphatidylinosiol 3 kinase (wortmannin and LY294002), protein tyrosine phosphorylation (herbimycin A, genistein, piceatannol, and for AMø only, PP2), and protein kinase C (staurosporine, Gö 6976, and calphostin C). Exposure of Mø to apoptotic or heat-killed thymocytes, but not to viable thymocytes, activated ERK1/2 rapidly, as detected by specific phosphorylation, but did not activate NF-κB or MAP kinases p38 or JNK. Mø phagocytosis of apoptotic T cells requires tyrosine, serine/threonine, and lipid phosphorylation. Mø recognition of apoptotic T cells triggers rapid but limited MAP kinase activation.
Regulation ofNRAMP1gene expression by 1α,25-dihydroxy-vitamin D3 in HL-60 phagocytes
Authors: Roig E A , Richer E , Canonne-Hergaux F , Gros P , Cellier M F M 
Published: September 2022

AbstractThe natural resistance-associated macrophage protein 1 (Nramp1) is a proton-dependent transporter of divalent metals. We studied NRAMP1 expression during HL-60 differentiation induced by VD and VD agonists. NRAMP1 and CD14 gene expression differed in kinetics of induction, mRNA levels and stability, and response to VD combined with PMA, whereas a combination of VD and IFN-γ induced similar up-regulation. NRAMP1 protein expression paralleled the accumulation of mRNA and was localized in the phagosomal membrane after phagocytosis. A promoter construct extending 647 bp upstream of NRAMP1 ATG showed myeloid-specific transcription in transient trasfection assays, which was up-regulated by VD in HL-60. In HL-60 clones stably transfected with this construct, transcription was apparently induced through indirect VD genomic effects, and there was accordance between the levels of reporter transcription and endogenous NRAMP1 mRNA in response to VD but not to IFN-γ. Thus, VD genomic effects stimulate NRAMP1 transcription and protein expression in maturing phagocytes.
Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages during acute endotoxemia
Authors: Ahmad Nosheen , Chen Li C , Gordon Marion A , Laskin Jeffrey D , Laskin Debra L 
Published: September 2022

AbstractEicosanoids generated via cyclooxygenase-2 (COX-2) and nitric oxide produced from inducible nitric oxide synthase (NOSII) have been implicated in endotoxin-induced tissue injury. In the present studies, we characterized COX-2 and NOSII activity in rat hepatic macrophages and their interaction during acute endotoxemia. Kupffer cells from control animals were found to constitutively express COX-2 and NOSII mRNA and protein. Whereas treatment of the cells with lipopolysaccharide (LPS) and/or interferon-γ (IFN-γ) had no major effect on COX-2, NOSII expression increased. Induction of acute endotoxemia resulted in a rapid and transient increase in constitutive COX-2 expression and prostaglandin E2 (PGE2) production by liver macrophages as well as NOSII expression and nitric oxide release. Cells from endotoxin-treated rats were also sensitized to generate more nitric oxide and express increased NOSII in response to LPS and IFN-γ. Inhibition of NOSII with aminoguanidine reduced COX-2 mRNA and protein expression as well as PGE2 production by activated macrophages from endotoxemic, but not control animals. In contrast, SC236, a specific COX-2 inhibitor, had no effect on NOSII mRNA or protein levels or on nitric oxide production by hepatic macrophages, even after endotoxin administration. These data suggest that activation of COX-2 may be important in the pathophysiological response of hepatic macrophages to endotoxin. Moreover, nitric oxide is involved in regulating COX-2 in activated liver macrophages during acute endotoxemia.
Immune escape of tumors: apoptosis resistance and tumor counterattack
Authors: Igney Frederik H , Krammer Peter H 
Published: September 2022

AbstractInteractions between the immune system and malignant cells play an important role in tumorigenesis. Failure of the immune system to detect and reject transformed cells may lead to cancer development. Tumors use multiple mechanisms to escape from immune-mediated rejection. Many of these mechanisms are now known on a cellular and molecular level. Despite this knowledge, cancer immunotherapy is still not an established treatment in the clinic. This review discusses the immune escape mechanisms used by tumors with an emphasis on mechanisms related to apoptosis.