bluuebunny/crossref_metadata_2025_split huggingface dataset:
Truncation of neurokinin-1 receptor—Negative regulation of substance P signaling
Authors: Spitsin Sergei , Pappa Vasiliki , Douglas Steven D 
Published: January 2018

AbstractSubstance P (SP) is a tachykinin peptide, which triggers intracellular signaling in the nervous and immune systems, as well as, other local and systemic events. The interaction between SP and its receptor, neurokinin-1 receptor (NK1R), results in major downstream cellular actions, which include changes in calcium fluxes, ERK, and p21-activated kinase phosphorylation and NFκB activation. Two naturally occurring variants of the NK1R, the full-length, 407 aa receptor (NK1R-F) and the truncated, 311 aa isoform (NK1R-T), mediate the actions of SP. Receptor truncation partially disrupts signaling motifs of the carboxyl tail, a critical site for mediating NK1R signaling, resulting in a “less-efficient” receptor. Although NK1R-F is the predominant isoform in the central and peripheral nervous systems, NK1R-T is expressed in several tissues and cells, which include monocytes, NK cells, and T-cells. The SP binding domain is not affected by truncation and this site is identical in both NK1R receptor isoforms. However, while cells expressing NK1R-F respond to nanomolar concentrations of SP, monocyte and macrophage activation, mediated through NK1R-T, requires micromolar concentrations of SP in order to elicit signaling responses. Elevated plasma levels of SP are associated with increased inflammatory responses and NK1R antagonists reduce inflammation and cytokine production in vivo. This mini review presents and discusses the novel hypothesis that the expression of NK1R-T on immune system cells prevents immune activation in a milieu, which usually contains low concentrations of SP and, thus, maintains immune homeostasis. In contrast, in the activated neuronal microenvironment, when SP levels reach the threshold at tissue sites, SP promotes immune activation and modulates monocyte/macrophage polarization.
Partial Characterization of a Mitomycin-C Resistant T Cell
Authors: Anderson Robert E , Standefer Jimmy C , Troup Gary M , Pogue Laura E 
Published: January 2018

Abstract
A cell resistant to concentrations of mitomycin-C associated with the inactivation of many in vitro immune responses is described. This cell is responsive to concanavalin A (Con A), poorly adherent to nylon wool, present in relatively greater numbers in lymph node than other lymphoid tissues, and is relatively radiosensitive. In part, the resistance of this T cell appears to relate to a reduced activity of a microsomal reductase responsible for converting mitomycin-C to its more active form. Discrepancies in reductase activity may represent a way to differentiate among subsets of lymphocytes.
In Vitro Control of Neutrophilic Phagocytosis of IgG-Coated SRBC by Macromolecules Involved in Released Products From Platelets
Authors: Sakamoto Haruhiko , Yokoya Yukihiro , Ooshima Akira 
Published: January 2018

Abstract
Analysis of macromolecular fraction of platelet release products (PRPr) was undertaken after we observed that pretreatment of human neutrophils with macromolecules (&gt;105 daltons) involved in PRPr enhanced phagocytosis of IgG-sensitized sheep red blood cells (IgG-SRBC). Sephadex G-200 gel filtration of PRPr revealed two macromolecular activators and two suppressors of neutrophilic phagocytosis of IgG-SRBC: MAPP(s), macromolecular activator(s) of phagocytosis from platelets; MSPP(s) macromolecular suppressor(s) of phagocytosis from platelets. The estimated molecular weights of the respective MAPPs were 100 kdaltons to 140 kdaltons (kd) (s-MAPP) and 200 kd to 290 kd (I-MAPP) and those of the respective MSPPs were 60 kd to 100 kd (s-MSPP) and 400 kd to 500 kd (I-MSPP). It is suggested that an l-MAPP molecule has at least an s-MAPP molecule as a functional unit and that MAPPs and larger MSPP (I-MSPP) might be glycoproteins, while smaller MSPP (s-MSPP) seems to contain neither carbohydrates nor lipids. As far as the effects of serum and plasma on phagocytosis of IgG-SRBC by neutrophils are concerned, the serum gave twice as much phagocytic activity as the plasma. Substantial MAPP-like activities were observed In the serum and MSPP-like activities were observed in both the serum and plasma.
Nitroblue Tetrazolium Reduction in Lymphocytes
Authors: Melinn Mary , McLaughlin Hugh 
Published: January 2018

Abstract
Certain populations of lymphocytes have been shown to reduce tetrazolium salts, indicating that superoxide anion may be present in lymphocytes. These experiments were done to determine if nitroblue tetrazolium reduction by lymphocytes was due to the presence of superoxide anion. Mitogen-activated lymphocytes showed increased nitroblue tetrazolium reduction compared to unstimulated cells, and the cells reducing nitroblue tetrazolium were both T-cells and non-T-cells. Release of superoxide anion or hydrogen peroxide by either resting or stimulated lymphocytes was not detected. There was no difference between resting and stimulated lymphocytes in the amount of chemiluminescence produced in the presence of lucigenin, an agent which appears to be sensitive to intracellular and extracellular superoxide anion. The results, then, indicate superoxide anion is not present in lymphocytes.
Low-Dose X-Irradiation and 4-Hydroperoxycyclophosphamide Distinguishes Three LYT-1+ Lymph Node T-Cell Subtypes That Respond to Specific Antigen In Vitro
Authors: Clark Connie , LaSota Irene , Borch Richard F 
Published: January 2018

Abstract
We investigated whether preculture exposure to low-dose X-irradiation and culture treatment with 4-hydroperoxycyclophosphamide (4-HPCY), a synthetic derivative of cyclophosphamide (CY), might distinguish subtypes of thymic-dependent (T) lymphocytes that respond to specific antigen in vitro. Lymph node (LN) cells were obtained from mice pretreated with CY and immunized with aggregated (A) human IgG (HGG) in Freund's complete adjuvant (CFA), and proliferation was assessed by incorporation of tritiated thymidine. Primed LN cells were untreated or exposed to low-dose irradiation before being cultured in medium alone and in medium containing 4-HPCY. The results show that these agents (irradiation and 4-HPCY) distinguished, in a dose-dependent manner, subtypes of T-cells which contribute to the specific antigen-stimulated proliferative response in vitro. For LN T-cells and LN Lyt-1 + T-cells, 20-25 rads and 1.0 μM 4-HPCY inactivated non-overlapping cell subtypes that respectively accounted for 26% and 28% of the response to HGG. The remaining 46% of HGG-responding cells were not affected by either agent. Although similar cell subtypes were discerned in unseparated LN cells, it required use of higher agent-doses. Cell cycle analysis revealed that treatment with irradiation, 4-HPCY, and the combination (both agents) caused S-phase arrest of 29%, 30%, and 55% of HGG-responding cells, respectively. Thus, identification of these cell subtypes could not be attributed to agent-mediated Inactivation of HGG-responding cells that might be in exclusively different phases of the cell cycle.
Detection of the Production of Oxygen-Centered Free Radicals by Human Neutrophils Using Spin Trapping Techniques: A Critical Perspective
Authors: Britigan Bradley E , Cohen Myron S , Rosen Gerald M 
Published: January 2018

Abstract
Human neutrophils generate oxygen reduction products as a consequence of membrane interactions with a number of stimuli. One oxygen-centered free radical (superoxide) has been uneqivocally shown to result from this “respiratory burst,” and some experimental evidence for another (hydroxyl radical) has been published, although debate remains as to its significance. The role of phagocyte-derived free radicals in microbicidal and tumoricidal activity as well as tissue damage at sites of inflammation has been the focus of extensive investigation in recent years. Of the techniques available to study free radical generation in biological systems, spin trapping has emerged as a powerful tool for detection and identification of these reactive species, owing in part to its ability to measure production of free radicals inside the phagosome. However, Interpretation of resulting spectra is extremely complex and filled with pitfalls and limitations. In this communication we review spin-trapping techniques and discuss the application of this system to the identification of free radicals resulting from stimulation of human neutrophils. Criteria are established which are necessary for definitive identification of superoxide and hydroxyl radical when employing this technology. In this context a critical perspective of previous studies of neutrophil-derived free radicals is offered.
Direct Visualization of Formylpeptide Receptor Binding on Rounded and Polarized Human Neutrophils: Cellular and Receptor Heterogeneity
Authors: Walter Robert J , Marasco Wayne A 
Published: January 2018

Abstract
We have used light microscope autoradiography to visualize binding of the formylhexa-peptide, N-formyl-norleucyl-leucyl-phenylalanyl-norleucyl-(125l)tyrosyl-lysine to rounded and spontaneously polarized human polymorphonuclear leukocytes. These cells possess receptors known to bind with high specificity and great avidity to the chemotactic formylpeptides. Cells adherent to glass slides were exposed to (125I)-hexapeptide at 4°, fixed, and autoradiographed. Hexapeptide binding was studied over the biologically active range of peptide concentrations varying from 0.63 nM to 10 nM and autoradiographic silver grains counted on 200 rounded or 50 polarized cells at each concentration. Examination of histograms plotted from these data revealed for rounded cells: 1) two major peaks at each concentration indicating the existence of two neutrophil subpopulations, the predominant subpopulation binding one-half as much formylpeptide (peak I) as the other (peak II); 2) progressively increasing proportions of cells in peak II as the free hexapeptide concentration increased. Accordingly, at 0.63 nM hexapeptide, peak II comprised only 8% of the total cell number, whereas at 10 nM, this peak represented 35% of the total cells. This suggested that different types of receptors may exist in the two cell subpopulations (high/low affinity or high/low negative cooperativity) and that these receptor types were expressed differentially on these subpopulations. Thus, cellular heterogeneity within the neutrophil population and receptor heterogeneity among hexapeptide receptors on an individual cell were both observed here. Each of these may significantly affect neutrophil functional responses to the chemotactic formylpeptides and may explain, at least in part, the curvilinearity in the Scatchard plots of formylpeptide receptor binding that has recently been reported.
At higher concentrations of peptide (5 nM), spontaneously polarized PMN bound hexapeptide more or less uniformly over the entire cell surface. However, at lower concentrations, hexapeptide binding was markedly shifted toward the cell anterior. As a group, polarized PMN bound similar total quantities of hexapeptide, as did rounded PMN at each peptide concentration tested. Receptors displaying high- and low-affinity characteristics were, however, distributed asymmetrically over the cell surface, with the high-affinity type receptors predominantly on the anterior one-half of the cell. Such an asymmetric distribution may serve to initiate or perpetuate cell locomotion.
Quantitative Studies of Human Monokine-Induced Endothelial Cell Elongation
Authors: FitzGerald Oliver M , Hess Evelyn V , Chance Arlene , Highsmith Robert F 
Published: January 2018

Abstract
Leucocyte-endothelial cell interactions are important in the inflammatory response. In this study, the effect of peripheral blood mononuclear cell (PBMC) products on endothelial cell (EC) shape was examined and quantified. PBMC were obtained from normal donors by Ficoll-Hypaque separation of heparinized whole blood and cultured for 72 hr in media containing 10% fetal calf serum with and without concanavalin A (Con A). Media conditioned by PBMC or control, nonconditioned media were then added to preconfluent, first passage EC cultures derived from human umbilical veins. Conditioned media from Con A-stimulated PBMC resulted in a dose-dependent, marked elongation and whorling of cultured EC. The minimum effective concentration found to elicit a response was 1.25%, with a maximum response occurring at 10%. Quantitative morphometric analyses of treated EC indicated that the elongation was highly significant (p &lt; 0.001) when compared to EC incubated with control, nonconditioned media. In addition, EC elongation was accompanied by a highly significant (p &lt; 0.001) increase in cell area. Although less dramatic, conditioned media from unstimulated PBMC also elicited a similar, significant dose-dependent change in EC shape. Significant changes in EC shape were evident within 6 hr and continued over the time course of the experiment (40 h). Cell shape changes were partially reversible at 18 h after removal of the PBMC-conditioned media and replacement with control, nonconditioned media. The change in EC morphology induced by a PBMC-derived factor(s) suggests a mechanism by which activated leucocytes may modulate cellular traffic at the blood-vessel wall interface.
Increased Adhesiveness of Complement-Stimulated Neonatal Calf Neutrophils and Its Pharmacologic Inhibition
Authors: Zwahlen Roland D , Slauson David O , Neilsen Nancy R , Clifford Charles B 
Published: January 2018

Abstract
Several in vitro functions of neonatal neutrophils (N-PMN) have been reported to be deficient and may be functionally related to the increased susceptibility of the newborn to infection. To evaluate an in vitro event corresponding to one of the early steps in the sequence of inflammation, we used zymosan-activated plasma as a source of activated complement fragments (Cf) and measured adherence of normal and Cf-stimulated bovine N-PMN to columns of Sephadex G-25. Adherence of control N-PMN and adult PMN (A-PMN) was comparable. When N-PMN and A-PMN were stimulated with a subaggregating dose of Cf, both responded with similar increases in adhesiveness. The stimulatory effect of Cf on N-PMN adhesiveness could be inhibited by pre-incubation of the N-PMN with either steroidal (0.05 mM dexamethasone) or non-steroidal (32 mM phenylbutazone) anti-inflammatory drugs. Ultrastructural observations correlated well with the results of the adhesiveness assays, and morphometric evaluation revealed an increase in the sectional circumference of Cf-stimulated N-PMN. Control cells were round with few short cytoplasmic projections, whereas Cf-stimulated cells exhibited marked shape irregularity, polarity, and prominent organelle-free lamellipodia development. There was a highly significant (P &lt; 0.001) increase in the measured circumference of Cf-stimulated cells. Thus, N-PMN were highly responsive to Cf stimulation, developed morphologic and functional changes indistinguishable from Cf-stimulated A-PMN, and were sensitive to pharmacologic inhibition.
Characterization of Surface Markers of Continuously Growing Murine Resident Macrophages
Authors: Muller Christian D , Lombard Yves , Bartholeyns Jacques , Poindron Philippe , Schuber Francis 
Published: January 2018

Abstract
Conditions have been described which allow an in vitro indefinite multiplication of differentiated murine macrophages (Lombard et al: Biol Cell 53, 219, 1985). R. and MAY-1 ceil lines, which were obtained, respectively, from mouse (Balb/c) spleen and resident peritoneal macrophages, have been further characterized. They present at their surface, besides the Mac-1 antigen and Fc-receptor, a mannose receptor which was characterized for its binding properties. This receptor Is responsive for a specific phagocytosis of mannosylated particles, i.e., mannosylated latex beads or oil droplets containing mannosylated bovine serum albumin. Moreover, R and MAY-1 ceils present an ectoenzyme profile (NAD+ glycohydrolase and nucleotide pyrophosphatase) similar to those of the corresponding resident macrophages.
Regulation by Interferon γ of Function in the Acute Monocytic Leukemia Cell Line, THP-1
Authors: Gaffney E V , Lingenfelter S E , Koch G A , Lisi P J , Chu C -W , Tsai S -C 
Published: January 2018

Abstract
THP-1 is an acute monocytic leukemia cell line which acquires phenotypic and functional monocytoid-like features following incubation with mezerein. The current study concerned the modulation of these features by rIFNγ. rIFNγ induces the time-dependent enhancement of HLA-DR expression in the presence or absence of mezerein but has no effect on the expression of Leu-M1, Leu-M2, or Leu-M3 antigens. CSF-1 production following mezerein activation was reduced by incubation in the presence of 103 and 104 units/ml rIFNγ. This was confirmed through both biological assays with mouse bone marrow cells and an indirect ELISA. In contrast, the concentration of growth inhibitory activity in conditioned medium was increased by rIFNγ. A small but significant increase in IL-1β concentration in conditioned medium was detected using a sensitive double-antibody ELISA and a radioimmunoassay. The results infer that the functional characteristics of this leukemia cell line are modulated by rIFNγ in a manner qualitatively similar to that reported for IFNγ treated normal monocytes.
Antigenic Variation and Macrophage Infiltration of Human Bladder Tumors Xenografted Into Nude Mice
Authors: Russell Pamela J , Philips Jeanette , Allan William , Hume David A 
Published: January 2018

Abstract
The presence of macrophages both within and around human bladder transitional cell carcinomas xenografted into nude mice has been examined using Immunocytochemical staining. Nine different xenograft lines derived from bladder tumors of eight patients were stained for F4/80, MHC II and PGP-1 labelled cells. The results revealed considerable heterogeneity both within and between tumors. All of the tumors generated some macrophage response at the tumor periphery, and this was marked in two instances, UCRU-BL-13, passage 9 and UCRU-BL-17, passage 2. In only two tumors was there substantial penetration of the tumor epithelium by macrophages, though infiltrating la+, F4/80+, PGP-1+ cells were sometimes seen spreading along the base of the epithelial sheets. Three of the tumors were characterized by the presence of L3T4+ T lymphocytes at the invasion front. The presence of macrophages or lymphocytes either at the invasion front or within the tumors did not correlate with the pathological grade of the tumors. PGP-1 monoclonal antibodies also stained granulocytes, which were present within the tumor mass in UCRU-BL-15, passage 2, possibly reflecting the production by the tumor of G-CSF. In addition, the PGP-1 antibodies stained some of the bladder tumors cells themselves, and, in some cases, the interstitial structures within the tumors. The significance of this staining is not yet understood. The xenografted tumors will provide a useful model to examine the constraints on tumor therapy using macrophage activating stimuli.
Diacylglycerols Modulate Human Polymorphonuclear Neutrophil Responsiveness: Effects on Intracellular Calcium Mobilization, Granule Exocytosis, and Superoxide Anion Production
Authors: Smith Robert J , Sam Laurel M , Justen James M 
Published: January 2018

Abstract
The synthetic diacylglycerols (DG), sn-1,2-dihexanoylglycerol (diC6), sn-1,2-dioctanoyl-glycerol (diC8), and 1-oleoyl-2-acetylglycerol (OAG) stimulated the release of granule constituents from and superoxide anion (Of) generation by human polymorphonuclear neutrophils (PMN). The DGs did not induce a rise in the cytosolic-free calcium concentration ([Ca2+]i), as monitored by the fluorescence of PMNs loaded with the fluorescent CA2+ indicator, Fura-2. DiC6, diC8, and OAG inhibited PMN degranulation elicited with the receptor-specific ligands, N-formyl-methionyl-leucyl-phenylalanine (FMLP), acetylsn-glyceryl-3-phosphorylcholine (AGEPC), and 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4) and the calcium ionophore, A23187. In contrast to their inhibitory effects on granule exocytosis, diC6, diC8 and OAG enhanced FMLP-, AGEPC-, LTB4 and A23187-stimulated O2- production. Activation of the respiratory burst with phorbol 12-myristate 13-acetate (PMA) was unaffected by the DGs. DiC8 inhibited the rise in [Ca2+]i elicited with FMLP, LTB4, and AGEPC; this effect, as well as the DG-mediated suppression of degranulation, could be reversed with the protein kinase C (PKC) inhibitor, 1-(-5-isoquinolinesulfonyl)-2-methylpiperazine hydrochloride (H-7). These data indicate that in addition to possessing the intrinsic capacity to activate PMNs, DG may function in a PKC-mediated autoregulatory mode to influence PMN activation in a response-specific manner by affecting certain components of receptor-coupled and receptor-independent signal transduction systems in a stimulus-specific manner.
SHORT COMMUNICATION: Bone Marrow Progenitors Cultured in the Presence of Granulocyte-Macrophage Colony-Stimulating Factor Versus Macrophage Colony-Stimulating Factor Differentiate Into Macrophages With Distinct Tumoricidal Capacities
Authors: Falk Lydia A , Hogan M Michele , Vogel Stefanie N 
Published: January 2018

Abstract
Bone marrow-derived cells from C3H/HeJ mice were cultured in the presence of recombinant murine granulocyte-macrophage colony-stimulating factor (rGM-CSF) or highly purified murine macrophage colony-stimulating factor (CSF-1) for 7 days. Following this 7-day culture period, mature macrophages were harvested and replated at precise densities in the absence of exogenous rGM-CSF or CSF-1, and assayed in a two-signal tumoricidal assay. Cultures were stimulated with medium only or with combinations of recombinant interferon-γ (rIFN-γ) as the “priming” signal, and/or butanol-extracted lipopolysaccharide (But-LPS) as the “triggering” signal for 24 hr. At this time, 51Cr-labeled, P815 tumor target cells were added, and the percent tumor cell cytotoxicity was determined after 16 hr. Macrophages derived under the influence of rGM-CSF exhibited significant tumoricidal capacity with medium alone (16 ± 5%). The addition of “priming” signal only (i.e., rIFN-γ, 10.0 U/ml) significantly increased tumoricidal capacity to 31 ± 9%. Treatment with But-LPS alone did not alter the basal tumoricidal activity of rGM-CSF-derived macrophages. Combinations of rIFN-γ (10.0 U/ml) and But-LPS (0.5–5.0 μg/ml) generated highly tumoricidal macrophages (50-60% tumor cell cytotoxicity). In contrast, medium-treated CSF-1-derived macrophages exhibited a significantly lower basal level of tumor cytotoxicity (6 ± 3%). Unlike rGM-CSF-derived macrophages, treatment of CSF-1-derived macrophages with high concentrations of rIFN-γ alone did not increase significantly the level of cytotoxicity above that of medium-treated cultures. However, CSF-1-derived macrophages responded to the highest concentrations of But-LPS (5.0 νg/ml) to increase tumoricidal activity from 6 ± 3% to 17 ± 5%. Optimal tumoricidal activity (44 ± 17%) was observed when CSF-1-derived macrophages were treated simultaneously with high concentrations of both rIFN-γ and But-LPS. Thus, macrophages derived from bone marrow progenitors in either rGM-CSF or CSF-1 exhibited tumoricidal capacities that differed in basal activity as well as in their requirements for and sensitivities to “priming” and “triggering” signals.