bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human tumor antigens recognized by T lymphocytes: implications for cancer therapy
Authors: Wang Rong-Fu , Rosenberg Steven A 
Published: January 2018

Abstract
The adoptive transfer of cytotoxic T lymphocytes (CTLs) derived from tumor-infiltrating lymphocytes (TIL) along with interleukin-2 (IL-2) into autologous patients with cancer resulted in the objective regression of tumor, indicating that these CTLs recognized cancer rejection antigens on tumor cells. In the past year, a number of such tumor antigens were isolated by the use of cDNA expression systems and biochemical approaches. The majority of tumor antigens identified to date have been found to be nonmutated, self proteins. This raises important questions regarding the mechanism of antitumor activity and autoimmune disease. Several tumor-specific mutated tumor antigens have also been recently identified, which include cell cyclin-dependent kinase 4 (CDK4) and β-catenin. For the first time, a novel human cancer antigen was recently found to be generated by the use of an alternative open reading frame of the previously identified tyrosinase-related protein-1 (TRP-1) gene. The identification of human tumor rejection antigens provides new opportunities for the development of therapeutic strategies against cancer. The potential clinical applications of these tumor antigens will be discussed.
Detection of mouse IL-8 receptor homologue expression on peripheral blood leukocytes and mature myeloid lineage cells in bone marrow
Authors: Wang Jian-bin , Zhang Yi , Kasahara Tadashi , Harada Akihisa , Matsushima Kouji , Mukaida Naofumi 
Published: January 2018

Abstract
Interleukin-8 (IL-8) exhibits activities on bone marrow progenitor cells such as regulation of their growth and their mobilization into peripheral blood. In order to clarify the molecular mechanism of the effects of IL-8 on mouse bone marrow cells, we examined the cellular distribution of mouse IL-8 receptor homologue by an immunofluorescence analysis. Peripheral blood Gr-1+ mature granulocytes, and a substantial portion of NK1.1+ natural killer cells in peripheral blood and spleen were stained positively with anti-mouse IL-8 receptor homologue antibody, whereas CD4+, CD8+, or B220+ lymphocytes in peripheral blood and spleen, and thymocytes were not. Moreover, a small portion of ER-MP20+ monocytes in peripheral blood but neither peritoneal resident nor bone marrow macrophages were stained with anti-IL-8 receptor homologue antibody. In bone marrow, mature granulocytes and to a lesser degree, metamyelocytes and myelocytes expressed IL-8 receptor homologue. Moreover, lineage marker (Lin)-c-kit+ bone marrow progenitor cells started to express IL-8 receptor homologue only 5 days after in vitro culture with IL-3 and stem cell factor when metamyelocytes and myelocytes appeared. These results indicated that myeloid lineage cells express a substantial number of IL-8 receptor homologues only at the stage of myelocytes.
CAP37, a neutrophil granule-derived protein stimulates protein kinase C activity in endothelial cells
Authors: Pereira H Anne , Moore Pete , Grammas Paula 
Published: January 2018

Abstract
CAP37 is a multifunctional protein isolated from human neutrophils with important implications in host defense and inflammation. It is antimicrobial, mediates monocyte chemotaxis, and binds endotoxin. The interaction of neutrophils with endothelial cells is a central feature in inflammation. The object of this study was to determine whether CAP37, a neutrophil-derived protein, could regulate vascular endothelial cell protein kinase C (PKC), an important signaling enzyme. We found that CAP37 stimulated endothelial PKC activity in both a time-and dose-dependent fashion. This stimulation was comparable in magnitude to that evoked by phorbol myristate acetate. A monospecific antiserum against CAP37 inhibited CAP37-induced PKC activity. To establish a structural basis for this activity, overlapping peptides, based on the sequence of native CAP37 were synthesized. Maximum PKC stimulation was evoked by a peptide corresponding to amino acids 95–122 of native CAP37. This domain was distinct from the antibiotic and endotoxin binding domain of the molecule, which resides between amino acids 20 and 44. These data demonstrate that CAP37 can alter endothelial cell PKC and suggest that CAP37 may (day a role in neutrophil-endothelial interactions.
Protein tyrosine phosphorylation in leukocyte activation through receptors for IgG
Authors: Santana Carla , Noris Gino , Espinoza Bertha , Ortega Enrique 
Published: January 2018

Abstract
Membrane receptors for the Fc portion of immunoglobulin G (IgG) antibodies (FcγRs) are expressed on almost every type of hematopoietic cells, where they mediate a wide variety of effector functions. A high degree of structural heterogeneity exists among FcγRs. The biological significance of such heterogeneity is unknown, since the structural diversity does not appear to be reflected in the binding specificity nor in the effector functions that each distinct receptor is able to mediate. Recent work has emphasized the essential role of protein tyrosine phosphorylation in the initiation of trans-membrane signaling by these receptors. In this article we review the role of protein tyrosine phosphorylation in signal transduction by the different types of FcγRs in order to assess to what extent the structural heterogeneity of this receptor family is related to different activation pathways utilized by each of its members.
The inhibitory effect of prostaglandin E2 on rat neutrophil aggregation
Authors: Wise Helen 
Published: January 2018

Abstract
Rat peritoneal neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP) produce an aggregation response that can be inhibited by prostaglandin E2 (PGE2) with an IC50 value of 2.6 10-9 M. Although PGE2 can stimulate [3H]cAMP production in neutrophils (EC50 4.3 10-8 M), the anti-aggregation response cannot be significantly attenuated by inhibitors of adenylate cyclase or protein kinase A, neither can it be potentiated by inhibition of phosphodiesterase activity. Despite these observations, it still remains possible that PGE2-mediated inhibition of rat neutrophil aggregation is a cAMP-dependent response mediated by highly localized changes in neutrophil cAMP. The inhibitory effect of PGE2 does not appear to depend on effects on intracellular calcium or KATP channels. Similarities exist between PGE2 and the profile of activity of phosphatidylinositol 3-kinase (PI 3-kinase) inhibitors, suggesting that PI 3-kinase is a possible target for PGE2 action in rat neutrophils.
Granzymes: a variety of serine protease specificities encoded by genetically distinct subfamilies
Authors: Smyth Mark J , O'Connor Michael D , Trapani Joseph A 
Published: January 2018

Abstract
Granzymes are a family of granule serine proteases found specifically in the cytotoxic granules of cytotoxic T lymphocytes and natural killer cells. Granzymes have features that are strongly conserved including: consensus sequences at their N-termini and around the three catalytic residues, activation from zymogenic forms, and conserved disulphide bridges. However, there is good genetic evidence to suggest that three distinct subfamilies of granzymes have coevolved. These subfamilies are most strikingly depicted by their distinct chromosomal loci and gene organization, dividing the granzyme family into subfamilies of the following: tryptases (human chromosome 5); chymotrypsinlike proteases (human chromosome 14); and a Metase amongst a cluster of elastase-like proteases (human chromosome 19). Modeling and mutational analysis has revealed that each subfamily of granzymes displays special sequence and structural features and a proteolytic specificity determined by subtle modifications to substrate binding pocket residues. It now remains of great interest to determine whether these subfamilies also possess distinct biological functions. Granzyme B has been shown to play an important role in lymphocyte-mediated target cell apoptosis and the tryptase, granzyme A, has been demonstrated to regulate the clearance of some pox virus infections. The future creation of other granzyme gene knockout mice should elucidate whether other chymotrypsin-like granzymes (C-H) also contribute to target cell apoptosis and whether the third subfamily member, natural killer cell-specific Metase, has a distinct biological function.
Infection by Candida albicans inhibits apoptosis of human monocytes and monocytic U937 cells
Authors: Heidenreich Stefan , Otte Britta , Lang Detlef , Schmidt Michael 
Published: January 2018

Abstract
Infectious microorganisms can differently induce or Inhibit apoptosis of immunocompetent effector and host cells. In this study we examined the influence of an infection by Candida albicans (C. albicans) on programmed cell death of monocytic U937 cells and human monocytes. Basal and tumor necrosis factor α (TNF-α)-induced DNA fragmentation of U937 cells was significantly inhibited by an infection with C. albicans. Enhanced apoptosis of U937 cells, induced by TNF-α, caused a diminished candidacidal activity of the effector cells, whereas inhibition of apoptosis by granulocyte-macrophage colony-stimulating factor (GM-CSF) was paralleled by an intensified host defense. Pretreatment of U937 cells or monocytes with the cyclooxygenase blocker indomethacin completely abolished the reduction of DNA fragmentation induced by the yeast. Studying the underlying mechanisms we found that C. albicans induced formation of prostaglandin E2 (PGE2) by U937. Exogenous administration of PGE2 down-regulated apoptosis of U937 or human monocytes to a similar extent as did fungal infection. Activation of protein kinase A by the cAMP analogue 8-bromo-cAMP inhibited U937 apoptosis, as did PGE2 On the other hand, rp-cAMP, a blocker of the cAMP-dependent signal transduction, restored and elevated DNA fragmentation levels down-regulated by C. albicans. U937 cells expressed the bcl-2 protein but the infection with fungi or PGE2 treatment did not increase proto-oncogene expression. Monocytic effector cells may therefore strengthen the defense against C. albicans by an autocrine feedback regulation via a PGE2-dependent, cAMP-transduced inhibition of apoptosis.
Dual effects of soluble CD14 on LPS priming of neutrophils
Authors: Troelstra Annet , Giepmans Ben N G , van Kessel Kok P M , Lichenstein Henri S , Verhoef Jan , van Strijp Jos A G 
Published: January 2018

Abstract
To evaluate the effect of soluble CD14 (sCD14) on human neutrophil response to lipopolysaccharide (LPS), we developed an LPS-priming assay that measures the chemiluminescence response to N-formyl-methionyl-leucyl-phenylalanine stimulation. Priming by 1 ng/mL rough LPS occurred in the presence of either serum or recombinant LPS-binding protein (LBP) only. Priming was completely CD14-dependent because preincubation of the neutrophils with an anti-CD14 monoclonal antibody prevented priming. We hypothesize that sCD14 enhances LPS response in neutrophils, but this response is not as effective as LPS response via membrane CD14 (mCD14). In our experiments sCD14 is present in an excess compared with mCD14. Priming of neutrophils occurs with low LBP, supposedly via sCD14-LPS complexes. With high LBP, addition of sCD14 inhibited LPS-priming of neutrophils. In that case, LPS may be transported to sCD14, preventing a more effective response via mCD14. In this study we demonstrate that the effect of sCD14 on neutrophil response to LPS is a delicate balance between activation and inhibition depending on concentration of serum or LBP.
Endothelial P-selectin and VCAM-1 each can function as primary adhesive mechanisms for T cells under conditions of flow
Authors: Konstantopoulos Konstantinos , Kukreti Sharad , Smith C Wayne , McLntire Larry V 
Published: January 2018

Abstract
This study demonstrates that endothelial P-selectin and vascular cell adhesion molecule 1 (VCAM-1), but not intercellular adhesion molecule 1 (ICAM-1), are capable of supporting extensive primary adhesion of T cells under flow. To address this issue, we used human umbilical vein endothelial cells (HUVECs) stimulated with histamine, interleukin-4 (IL-4), or interferon-γ (IFN-γ) that provide essentially a P-selectin, VCAM-1, or ICAM-1 surface, respectively, in a physiologically relevant cell type. Monoclonal antibody (mAb) blockade studies were carried out to confirm the specificity of these adhesive interactions and rule out a number of other potentially important adhesion molecules. Quantitation of adhesion showed that almost all of the interacting T cells rolled on histamine-stimulated HUVECs or CHO-P cell monolayers. In contrast, 20% of the total interacting T cells with 24-h IL-4-treated HUVECs were firmly adherent. mAb blocking experiments revealed that T cell adhesion to IL-4-treated HUVECs is α4-VCAM-1 dependent. Furthermore, mAb 4B9 directed against domain 1 of VCAM-1 eliminated adhesion, suggesting that α4 integrins may not interact with either the alternatively spliced domain 4 of VCAM-1 or fibronectin in this process. At a wall shear stress of 2 dyn/cm2, the mean T cell rolling velocities were significantly lower on 24-h IL-4-activated HUVECs (10.2 ± 2.6 μm/s) compared with either CHO-P cells (15.6 ± 3.1 μm/s) or histamine-stimulated HUVECs (16.6 ± 6.1 μm/s). ICAM-1, expressed on the surface of 24-h IFN-γ-activated HUVECs pretreated with an anti-VCAM-1 mAb to eliminate any VCAM-1-dependent contribution, did not support T cell adhesion under shear conditions. Together these data indicate that T cell primary adhesion can be mediated by both endothelial P-selectin and VCAM-1 but not ICAM-1. α4 integrins are highly versatile molecules, capable of initiating T cell rolling interactions and mediating firm arrest on activated endothelium.
CD40-CD40L interactions provide “third-party” costimulation for T cell response against B7-1-transfected human breast tumor cells
Authors: Pericle Federica , Epling-Burnette P K , Podack Eckhard R , Wei Sheng , Djeu Julie Y 
Published: January 2018

Abstract
In this study we provide evidence that a human breast carcinoma cell line, MDA-MB-231 (MDA), can be made immunogenic following B7 transfection and that fall T cell activation is obtained through cooperation of T-B lymphocytes via CD40-CD40L interactions. Tumor cells transfected with either B7 gene (MDAB7), neomycin-resistant gene only (MDAneo), or untransfected (MDA) were used in an allogeneic mixed lymphocyte tumor culture (MLTC) to investigate their ability to stimulate T cell proliferation and generate cytotoxic T lymphocytes (CTL). MDAB7 induced moderate T cell proliferation while MDAneo or MDA did not. Substantial T cell proliferation and de novo generation of cytolytic T cells was obtained only in response to MDAB7 when B cells were present during the MLTC. CD8+-purified T + B cells proliferated to a greater extent than whole T cell populations + B or CD4+ + B in response to MDAB7. Addition of (α-B7-1 or α-CD40 in the MLTC inhibited T cell proliferation by 65 and 40%, respectively, whereas T cell proliferation and generation of CTL was completely abrogated when MLTC was performed in the presence of both antibodies. These data suggest that the engagement of CD40L on T cells with CD40 on B cells provides a costimulatory signal which, in synergism with TCR-dependent MDAB7-T cell recognition (signal 1) and B7/CD28 interactions (signal 2), leads to full T cell activation.
Evidence for an enhanced transcription-dependent de novo synthesis of C/EBPβ in the LPS activation of the chicken lysozyme gene
Authors: Goethe Ralph , Phi-van Loc 
Published: January 2018

Abstract
C/EBPβ has been shown to mediate the lipopolysaccharide (LPS)-induced expression of the lysozyme gene through enhanced binding to the – 6.1-kb lysozyme enhancer. In this study, we describe the LPS regulation of the C/EBPβ gene in myelomonocytic HD11 cells. Northern analysis showed that the steady state level of C/EBPβ mRNA increased in response to LPS. The half life of C/EBPβ mRNA of about 1 h in HD11 cells was not affected by exposure to LPS. Nuclear run-on transcription experiments with isolated nuclei revealed that the rate of C/EBPβ gene transcription was enhanced by LPS, demonstrating that the C/EBPβ gene in HD11 cells was regulated at the transcriptional level in response to LPS. Furthermore, the LPS-induced binding activity of C/EBPβ to the – 6.1-kb lysozyme enhancer was dependent not only on protein synthesis, but also on transcription. Thus, these results suggested that the LPS-induced binding activity to the – 6.1-kb lysozyme enhancer in HD11 cells was regulated by an enhanced transcription-dependent de novo synthesis of C/EBPβ.
Involvement of leukotrienes, TNF-α, and the LFA-1/ICAM-1 interaction in substance P-induced granulocyte infiltration
Authors: Saban Marcia R , Saban Ricardo , Bjorling Dale , Haak-Frendscho Mary 
Published: January 2018

Abstract
Substance P (SP) has been shown to mediate granulocyte infiltration into the mouse skin by inducing mast cell degranulation. In this study, using a variety of specific inhibitors, we investigated the cascade of events involved in the response of neutrophils and eosinophils to SP. The prostaglandin inhibitor, indomethacin, had little effect on SP-induced leukocyte migration. In contrast, pretreatment with the leukotriene (LT) synthesis inhibitor, A-64077, completely blocked neutrophil but not eosinophil migration in response to SP. Participation of tumor necrosis factor α (TNF-α) and LFA-1/ICAM-1 interaction was confirmed by inhibition of SP-induced leukocyte migration by pretreatment of mice with monoclonal antibodies to TNF-α, LFA-1, and ICAM-1. Moreover, alteration in leukocyte migration by indomethacin was found to depend on the concentration of TNF-α used. Indomethacin did not alter the number of leukocytes induced by low concentrations of TNF-α (0.1 ng), but reduced the number of cells stimulated with high TNF-α concentrations (1.0 ng). These results support the concept that SP modulates in vivo neuroinflammatory responses, as measured by granulocyte migration, initiating a cascade of events that includes LT production, TNF-α secretion, and engagement of LFA-1 and ICAM-1.
Leukocyte activation induces surface redistribution of P-selectin glycoprotein ligand-1
Authors: Bruehl Richard E , Moore Kevin L , Lorant Diane E , Borregaard Niels , Zimmerman Guy A , McEver Rodger R , Bainton Dorothy F 
Published: January 2018

Abstract
Binding of P-selectin on activated endothelium to P-selectin glycoprotein ligand-1 (PSGL-1) on neutrophils mediates the initial tethering and rolling of neutrophils on the vessel wall at inflammatory sites. Upon activation of rolling cells by locally expressed signaling molecules, integrin-dependent adhesion mechanisms are engaged and transendothelial migration proceeds. P-selectin binding sites are uniformly distributed on the surface of quiescent neutrophils, but are redistributed to the uropod of activated neutrophils. It is unclear whether this activation-induced change in the surface topography of P-selectin binding sites is due to surface redistribution of PSGL-1, shedding of PSGL-1 from the lamellapod, and/or movement of PSGL-1 from an intracellular compartment to the uropod of the polarized cell. With the use of immunogold electron microscopy we previously demonstrated that PSGL-1 was localized to the tips of microvilli on neutrophils. Here we document a similar localization for PSGL-1 on eosinophils, basophils, monocytes, and lymphocytes. On quiescent neutrophils, 80% of the PSGL-1 label was on tips of microvilli, which are randomly distributed around the cell circumference. On activated, polarized neutrophils, the PSGL-1 label was restricted to a segment of 42% of the cell circumference even though total labeling decreased by only 26%. Latex microbeads coated with anti-PSGL-1 mAb bound preferentially to the uropod of activated neutrophils. Subcellular fractionation and immunogold analysis of frozen thin sections of neutrophils failed to detect PSGL-1 in any intracellular compartment. Taken together, these data indicate that the activation-induced change in the surface topography of PSGL-1 is due to surface redistribution of PSGL-1. This process may facilitate transendothelial migration by disrupting bonds between P-selectin and PSGL-1 at the leading edge of migrating cells.
Monocytic-endothelial cell interaction: regulation of prostanoid synthesis in human coculture
Authors: Koll Sylvia , Goppelt-Struebe Margarete , Hauser Ingeborg , Goerig Matthias 
Published: January 2018

Abstract
Coculture of a monocytic cell line (HL-60) and iliacal endothelial cells as an in vitro model of vascular inflammation was investigated for cooperative regulatory mechanisms of prostanoid synthesis under conditions of selective prestimulation. In coculture of endothelial cells and 12-O-tetradecanoylphorbol 13-acetate (TPA) -prestimulated monocytic HL-60 cells the capacity of prostanoid synthesis from arachidonic acid was strongly increased compared with monocultures. Concomitant with upregulation of specific adhesion molecules, cyclooxygenase (COX) 2 mRNA was induced in endothelial cells in coculture independent of cell contact. HL-60 cells exhibited no alterations in mRNA expression of cyclooxygenases or thromboxane synthase. Coculture of TPA-prestimulated endothelial cells with unstimulated HL-60 cells led to a selectively increased capacity of thromboxane production. Under this condition HL-60 cells upregulated COX1 and COX2 mRNA, whereas endothelial mRNA levels did not change. Our data demonstrate that the increase in prostanoid synthesis in coculture essentially depends on rapid induction of COX2 mRNA within 2 h.
Timing of prostaglandin exposure is critical for the inhibition of LPS- or IFN-γ-induced macrophage NO synthesis by PGE2
Authors: Harbrecht B G , Kim Y-M , Wirant E A , Simmons R L , Billiar T R 
Published: January 2018

Abstract
Macrophage nitric oxide (NO) synthesis is an integral component of the host defense system. We have previously found that NO and prostaglandins interact in a variety of ways. NO modulates Kupffer cell prostaglandin E2 (PGE2) production and we have recently described the inhibitory effects of PGE2 on NO synthesis in both Kupffer cells and hepatocytes. Activated macrophages produce a number of prostaglandins but studies regarding the capacity of prostaglandins to regulate macrophage NO synthesis have yielded conflicting results. We found that exogenous PGE2 decreased lipopolysaccharide (LPS)-induced NO synthesis in murine resident peritoneal macrophages and in the RAW 264.7 murine macrophage cell line. PGE2 also suppressed NO synthesis in response to interferon-γ (IFN-γ) alone and a combination of LPS + IFN-γ. Inhibition of endogenous PGE2 synthesis with indomethacin or ibuprofen had no effect on NO synthesis. PGE2 added with the activating stimulus was most effective. PGE2 lost the capacity to block NO synthesis if added more than 180 min after LPS. PGE2 decreased inducible NO synthase (iNOS) mRNA and immunoreactive iNOS protein, consistent with the hypothesis that exogenous PGE2 inhibits macrophage iNOS expression but that the inhibition depends on the time and concentration of prostaglandin exposure.