bluuebunny/crossref_metadata_2025_split huggingface dataset:
6-Trans-Leukotriene B4 Is a Neutrophil Chemotaxin in the Guinea Pig Dermis
Authors: Fretland Donald J , Widomski Deborah L , Anglin Charles P , Walsh Robin E , Levin Stuart , Gaginella Timothy S 
Published: January 2018

Abstract
The products of the 5- and 12-lipoxygenase (5-LO, 12-LO) pathways of arachidonic acid metabolism are implicated as proinflammatory mediators in a number of disease states. 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] is present in large quantities in human psoriatic lesional skin and can be further metabolized by 5-LO to 5(S),12(R)-dihydroxy-(6E,8Z,10E,14Z)-eicosatetraenoic acid (6-trans-LTB4). Furthermore, leukotriene B4 (LTB4) and the sulfidopeptide leukotrienes (LTC4, LTD4) can be transformed to 6-trans-LTB4. When injected into the guinea pig dermis, 6-trans-LTB4 (1.0,10.0,20.0 μg/intradermal site) caused a significant (P &lt; 0.02) infiltration of polymorphonuclear leukocytes (PMN) at 4 hr as assessed by histology and the levels of the PMN marker enzyme myeloperoxidase. 6-Trans-LTB4 is a more potent PMN chemoattractant than 12(R)-HETE in the guinea pig dermis but is far less potent than LTB4. Pharmacological interdiction of leukotriene production or receptor binding should take into account the proinflammatory activity of 6-trans-LTB4.
Tumor Necrosis Factor Increases In Vivo Glucose Uptake in Hepatic Nonparenchymal Cells
Authors: Spolarics Zoltán , Schuler Ágnes , Bagby Gregory J , Lang Charles H , Mészáros Károly , Spitzer John J 
Published: January 2018

Abstract
This study aims to elucidate the in vivo metabolic response of different liver cells following a short-term (30 min) infusion of a nonlethal dose of human recombinant tumor necrosis factor (TNF). In vivo glucose uptake of different tissues and isolated liver cells was determined by a sequential double-labeling version of the tracer 2-deoxyglucose technique. Following TNF administration glucose uptake was increased in the liver, lung, spleen, and skin while it was not changed in muscle and testis. In response to TNF infusion neutropenia developed which was sustained for 40 min. The number of lymphocytes in the blood was also decreased after the termination of TNF infusion. This short-term infusion of TNF, however, was not accompanied by marked sequestration of leukocytes into the liver. In vivo glucose uptake in response to TNF was doubled in the Kupffer cells and increased by 56% in hepatic endothelial cells. Glucose uptake of parenchymal cells was not significantly affected. The prompt increase of glucose uptake in the reticuloendothelial cells of the liver, primarily in the Kupffer cells, following TNF administration suggests that a similar metabolic response of these cells to sepsis may be mediated at least in part by TNF. It is suggested that the increased glucose uptake by the hepatic nonparenchymal cells is a reflection of the immunmodulatory effect of TNF.
Function and Regulation of the Murine Lymphocyte CD2 Receptor
Authors: Abraham D J , Bou-Gharios G , Beauchamp J R , Plater-Zyberk C , Maini R N , Olsen I 
Published: January 2018

Abstract
The CD2 receptor on T-lymphocytes plays a major part in mediating adhesive interactions via the LFA-3 ligand and in transducing signals for lymphocyte activation. In this study the expression, function, and internalization of the CD2 receptor was investigated in resting and activated murine T-cells. Surface iodination of intact lymphocytes showed that both types of cell expressed this antigen as a single polypeptide of 63 KDa, and flow cytometry analysis demonstrated that there was four times as much CD2 on lymphoblasts as on resting cells. Moreover, the CD2 receptor had a more prominent role in the adhesion of the activated lymphocytes to extravascular cells than in the binding of resting cells. Only activated lymphocytes internalized CD2, in the presence or absence of the anti-CD2 monoclonal antibody (mAb) 12-15, more than 80% of the 12-15/CD2 complex being removed from the cell surface within 24 hr. Application of 125l-labelled mAb 12-15 followed by subcellular fractionation on Percoll gradients showed that the complex was internalized initially into a low-density compartment and subsequently transported to heavy-density organelles, in which it was degraded. Immunogold electron microscopy revealed that immediately after the initial binding of mAb 12-15 to the lymphoblasts, the gold particles were localized in clusters exclusively at the plasma membrane. After a short period of culture, the mAb 12-15/CD2 complex was detected in small vesicles near the cell surface. Immunogold staining for a lysosomal enzyme β-glucuronidase (Gus), for the lysosomal membrane protein LAMP-1, and for the mannose 6-phosphate targetting receptor (MPR) showed that the complex was transported from the endosomal compartment to lysosomal organelles in the activated T-cell. Although mAb 12-15 bound to CD2 in resting T-lymphocytes, in these cells the complex remained associated with the plasma membrane compartment only, even after prolonged culture. These data show that activated but not resting lymphocytes endocytosed the receptor, thereby regulating the expression of this antigen at the plasma membrane. This suggests that the endocytic and lysosomal compartments of lymphocytes have major roles in immune functions, by controlling the level of receptors at the lymphocyte cell surface and thus their response to cytokines and inflammatory mediators as well as their direct interaction with other cells.
Priming of Rabbit Alveolar Macrophages for Enhanced Oxidative Responses by Herpes Simplex Virus Type 2 Infection
Authors: Giridhar G , Hayakawa H , Kucera L S , Myrvik Q N 
Published: January 2018

Abstract
The effect of herpes simplex virus type 2 (HSV-2) infection on the oxidative response in infant and adult rabbit alveolar macrophages (AM) was studied using either phorbol myristate acetate (0.5 μg PMA/ml) or latex (250 μg/ml) as eliciting agents in a chemiluminescence (CL) assay. Results indicated that uninfected infant AM responded to a latex-elicited but not PMA-elicited CL response. HSV-2 infection (moi=1.0) of infant AM for 2 hr at 37° did not alter the PMA or latex-elicited CL responses. In contrast, uninfected adult AM exhibited a markedly increased CL response when elicited with either PMA or latex. HSV-2 infection (moi=1) of adult AM for 2 hr further increased both PMA- and latex-elicited CL responses. Increasing the moi to 10 inhibited both PMA- and latex-elicited CL responses. Incubation of uninfected control and HSV-2 infected adult AM for 18 hr at 37° resulted in spontaneous priming of the cells for increased CL responses. In the absence of PMA HSV-2 alone failed to elicit a CL response in adult AM. Infection with heat-inactivated HSV-2 (moi=1.0 before heat inactivation) did not prime adult AM for enhanced CL responses. AM from BCG immunized adult rabbit produced a considerably higher level CL response that nonimmunized AM; however, HSV-2 infection of these cells did not further enhance the response. In summary, these data indicate that adult AM but not infant AM can be primed by active HSV-2 infection for an increased CL response elicited by either PMA or latex.
On the Mechanism of Antiinflammation Induced by Tumor Transplantation, Surgery, and Irritant Injection
Authors: Normann S , Besedovsky H , Schardt M , del Rey A 
Published: January 2018

Abstract
Tumor transplantation, major surgery, and injection of nonspecific irritants elicit inflammation locally while suppressing inflammation induced subsequently and at distant sites. Such systemic antiinflammation in rodents occurs via corticosterone-independent and -dependent pathways. Based upon hormone measurements and the response to adrenalectomy, antiinflammation induced by irritants and certain surgical procedures is corticosterone independent while that which follows tumor transplantation is corticosterone dependent. However, injection of tumorous ascites stimulates both pathways since it contains two antiinflammatory factors: Factor A (molecular weight &lt;2,000) does not alter hormone balance while Factor B (molecular weight 30,000–100,000) increases corticosterone levels and is corticosterone dependent. Desensitization of systemic antiinflammation develops rapidly regardless of whether it is corticosterone dependent (Factor B) or independent (Factor A or irritants). However, tumor transplantation resists desensitization possibly by inducing an immune response since lymphocytic mitogens prevent development of and break established desensitization. Nevertheless, abolition of tumor-induced antiinflammation follows injection of tumorous ascites by a mechanism that involves Factor B suppression of the corticosterone response to the tumor while Factor A apparently raises the threshold at which physiological increases in corticosterone inhibit leukocyte emigration. We conclude that systemic antiinflammation is a general consequence of a localized inflammatory reaction and that desensitization of such antiinflammation develops rapidly. Recent evidence indicates that certain mediators of inflammation are proinflammatory when administered intradermally but antiinflammatory when given intravenously. Thus, systemic antiinflammation may arise when chemical mediators of inflammation generated by a local reaction gain access to the circulation.
Maintenance of Human Immunodeficiency Virus Type-1 Proviral DNA in Human Fetal Dorsal Root Ganglia Neural Cells Following a Nonproductive Infection
Authors: Kunsch Charles , Wigdahl Brian 
Published: January 2018

Abstract
Infection of the nervous system by human immunodeficiency virus type-1 (HIV-1) has been implicated in the generation of acquired immunodeficiency syndrome (AIDS)-associated neurologic dysfunction and direct infection of glia has been suggested as one of the potential mechanisms leading to deterioration of nervous system function. We have been examining the interaction of HIV-1 with the developing peripheral nervous system in vitro, and have previously shown that HIV-1 infection of primary human fetal dorsal root ganglia (DRG) neural cells resulted in HIV-1 gag antigen expression in approximately 70% of the glial cell subpopulation with little, if any, cytopathic damage to the infected cells. Accumulation of HIV-1 gag antigens and viral mRNA reached a maximum by 2–3 days postinfection and declined thereafter to minimally detectable levels in the surviving neural cell population. In addition, infection of the fetal DRG neural cells appeared to be abortive or nonproductive, with little if any, infectious progeny virus production. However, we have been able to detect HIV-1-specific proviral DNA as late as 24 days postinfection by polymerase chain reaction amplification and subsequent DNA blot hybridization. These results suggest that accumulation of HIV-1 structural proteins without the assembly and release of mature virus in HIV-1-infected human fetal DRG neural cells results in a nonproductive infection and maintenance of HIV-1 proviral DNA in the infected cell population.
rTNFα Facilitates Human Polymorphonuclear Leukocyte Adherence to Fibrinogen Matrices With Mobilization of Specific and Tertiary but Not Azurophilic Granule Markers
Authors: Hanlon W A , Stolk J , Davies P , Humes J L , Mumford R , Bonney R J 
Published: January 2018

Abstract
rTNFα facilitates highly reproducible adherence of polymorphonuclear leukocyte (PMN) to fibrinogen-coated surfaces in a concentration- and time-dependent manner. The adhesion was maximal with 1.0 nM rTNFα within 40–50 min at 37°C. A monoclonal antibody (1B4) directed toward the β2-chain of the integrin receptor for fibrinogen (CD11b, CD18) completely inhibited the rTNFα induced adhesion. TNFα caused a time-dependent secretion of the granule markers gelatinase and lactoferrin but no liberation of myeloperoxidase and minimal production of Aα(1–21), a specific cleavage product of fibrinogen generated by elastase, as markers for the azurophilic granule. PMN adhered to fibrinogen in the presence of rTNFα could be further stimulated with cytochalasin B and N-formyl-methionyl-leucyl-phenylalanine (FMLP) to release azurophilic granule markers as measured by increasing MPO activity and Aα(1–21) production over time. Thus the rTNFα-facilitated adherence of PMN to a fibrinogen matrix provides a system for partial activation of PMN resulting in release of markers of specific and tertiary but not azurophilic granules. Moreover, these conditions should provide an opportunity to define more clearly the signal transduction processes involved in azurophilic granule release.
Effect of Chronic Endotoxemia on Concanavalin A-Stimulated Inositol Lipid Metabolism in Rat Splenocytes
Authors: Hagar Arthur F , de Turco Elena B. Rodriguez , Spitzer Judy A 
Published: January 2018

Abstract
The effect of a chronic, noniethal infusion of endotoxin (ET) on the phosphatidylinositol (PI) cycle in rat splenocytes was evaluated. Rats were infused intravenously with sterile saline or Escherichia coli ET (0.1 mg/ 100 g body weight/ 24 hr) for 30 hr via subcutaneously implanted osmotic pumps. The splenocytes were then labeled in vitro for 90 min with [32P]PO4 or for 3 hr with [3H]myoinositol to assess the status of the resynthesis and degradative parts of the PI cycle, respectively. PI cycle activity was depressed in splenocytes of ET-infused rats as evidenced by a 25% reduction in the incorporation of [32P]PO4 into phosphatidic acid (PA), PI, and the polyphosphoinositides and by a similar decrease in the production of [3H]inositol phosphates. Stimulation of splenocytes with concanavalin A (Con A) resulted in dose-dependent increases in the incorporation of [32P]PO4 into PA and PI and in the production of [3H]inositol phosphates, indicating that Con A stimulates the PI cycle in these cells. The Con A-stimulated increase in inositol phosphate production was higher in splenocytes from ET-infused rats. We have previously shown that splenocytes from rats infused for 30 hr with ET exhibit a decreased blastogenic responsiveness to Con A and lipopolysaccharide [Spitzer et al., Proc. Soc. Exp. Biol. Med. 186,27,1987]. The present data do not support the notion that inositol lipid-mediated signaling mechanisms are solely responsible for the expression of the appropriate functional response and suggest that in ET-infused rats there is an uncoupling of the initial response to Con A (i.e., the production of inositol lipid-derived second messengers) and the long-term (i.e., mitogenic) response.
A Method for the Quantitative Analysis and Standardization of Interleukin-1 Bioactivity
Authors: Krakauer Teresa , Krakauer Henry 
Published: January 2018

Abstract
A method is presented for the reproducible quantitation of the biological activity of interleukin 1 (IL-1). This method provides diagnostic tools which give insights into the qualitative aspects of the binding of IL-1 and of the resulting activation of the responder thymocytes; for example, whether the lymphokine and/or the responder population is heterogeneous, or whether a threshold level exists. It establishes under what circumstances the assumptions on which it is based are reasonably adhered to and, consequently, quantitative estimation in the manner it prescribes is justified. It also gives a simple way to calculate both the maximal response attainable for each preparation in an assay and the dilution of a particular preparation that would produce a half-maximal response, the accepted unit of activity of IL-1. This empirical technique provides an improved means of comparing the activities of various preparations of IL-1 in bioassays using various stocks of responder cells and reagents. It should also be applicable to the evaluation of the biological activity of lymphokines in general.
Tumor-Associated Macrophages Share In Vitro Growth Characteristics With Resident but not Elicited Macrophages
Authors: Reed Doug , Burnham Kim 
Published: January 2018

Abstract
Recent studies have shown that tissue macrophages are capable of proliferation and that this capability is enhanced by various cytokines, including macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Tumor-associated macrophages (TAM) have been demonstrated to proliferate in vitro, but no information is currently available on the ability of M-CSF and GM-CSF to enhance this response. To address this problem, limiting dilution analysis was utilized to examine the proliferative ability of macrophages isolated from two murine tumors of distinct origin following growth in secondary hosts. As a means of comparison, resident peritoneal macrophages (RPM) and thioglycolate-elicited macrophages (TEM) were also analyzed. Results indicate that a rare subset of TAM and RPM is capable of proliferation and that M-CSF and GM-CSF enhance the frequency of TAM and RPM which proliferate, but do not enhance the growth of TEM.
Genetic Resistance/Susceptibility to Mycobacteria: Phenotypic Expression in Bone Marrow Derived Macrophage Lines
Authors: Radzioch D , Hudson T , Boulé M , Barrera L , Urbance J W , Varesio L , Skamene E 
Published: January 2018

Abstract
Congenic strains of mice susceptible (B10A.Begs) or resistant (B10A.Bcgr) to BCG were established. Here we describe the model system which has been established to analyze the functional activities of macrophages in the two strains. We have immortalized bone marrow macrophages from B10A.Bcgs and B10A.Bcgr congenic strains of mice and derived cloned macrophage lines designated B10S and B10R, respectively. B10R and B10S cell lines exhibited surface markers and morphology typical of macrophages. B10S and B10R were similar in their phagocytic activity, in their level of c-fms, in their transforming growth factor β (TGFβ) mRNAs expression, and in their expression of tumoricidal activity in response to interferon-gamma (IFNγ) plus lipopolysaccharides (LPS). However, B10R macrophages expressed a higher level of la mRNA when activated with IFNγ compared with B10S macrophages. Analysis of the bacteriostatic activity of the two cell lines revealed that B10R macrophages were much more active in inhibiting Mycobacterium smegmatis replication than B10S. To measure the intracellular destruction of bacilli, a bactericidal assay based on hybridization with an oligonucleotide probe specific for mycobacterial ribosomal RNA was designed. The results demonstrated that B10R macrophages were endowed with enhanced constitutive bactericidal activity as compared with B10S.
In conclusion we have obtained macrophage lines from bone marrow of B10A.Bcgs and B10A.Bcgr mice that express to a similar extent functional and phenotypic characteristics of macrophages. However, we demonstrate that relative to B10S macrophages, the B10R macrophages have higher expression of la mRNA and that they are constitutively more active in expressing mycobactericidal activity.
Dynamics of Human Neutrophil Aggregation Evaluated by Flow Cytometry
Authors: Rochon Yvan P , Frojmovic Mony M 
Published: January 2018

Abstract
In order to directly monitor neutrophil aggregation, we have developed a simple particle counting technique using flow cytometry. Flow times were used to determine aggregation from changes in the total number of particles per unit volume (%PAT), while fluorescent signals emitted from glutaraldehyde-fixed neutrophils were used to measure changes in the total number of singlet neutrophils (%PAgs). Flow cytometrically-determined %PA values were found to be virtually identical to values determined from microscopy. We show that aggregation parameters can be evaluated and compared simply from measures of changes in total particle count without a need for distinguishing singlets from murtiplets. A number of aggregation parameters are introduced and related to the initial cell concentration (No) and stir speed (shear). Aggregation of neutrophils, following stimulation with 0.5 μM FMLP (N-formyl-methionyl-leucyl-phenylalanine), showed a latent time (ti) of 4 ± 1.5 sec independent of No or stir speed; had a forward rate of aggregation (v,) which was proportional to the initial cell concentration and the stir speed; plateaued for ≥ 60 s; and showed partial to complete reversal by 7.5 min. Above a critical stir speed, the extent and duration of aggregation varied inversely with the stir speed. The stir and No dependence of the aggregation parameters studied suggest the existence of subpopulations of neutrophils with distinct efficiencies of aggregation.
Regulation of Complement 5a Receptor Expression in U937 Cells by Phorbol Ester
Authors: Rubin Janet , Titus Louisa , Nanes Mark S 
Published: January 2018

Abstract
Receptors for the anaphylactic portion of complement, C5a, are not initially expressed in the monoblastic U937 cell line, but appear as the cell is induced to differentiate by the synergistic actions of 1,25(OH)2D and cyclic adenosine monophosphate (cAMP). Phorbol myristate acetate (PMA), which activates the protein kinase C pathway (PKC), does not cause C5a receptor (C5aR) expression when used as a single agent. The induction of C5aR by the synergistic actions of 1,25(OH)2D and cAMP, however, can be augmented as much as 180% by the addition of PMA. C5aR arising in cells exposed to 1,25(OH)2D and 8,4-chlorophenylthio-cAMP have an affinity constant of about 0.4 nM as assessed by cold competition analysis. We show here that when phorbol augmentation of receptor number occurs, the affinity constant is increased by 3.6-fold. In an effort to ascertain whether the change in C5aR Kd involved a PKC-dependent event we examined whether 5–60 min exposure of C5aR-positive cells to PMA would change C5aR Kd. Acutely, PMA caused a downregulation of receptor binding with decreases in apparent receptor number out of proportion to changes in Kd. One hundred nanomolar PMA, which effects nearly complete translocation of PKC to the membrane, consistently caused a 70–90% decrease in C5a surface binding. This downregulation was proportional to PMA dose and exposure time. Micromolar concentrations of the microtubule depolymerizing agents colchicine and vinblastine caused a less drastic downregulation, about 50% of the maximal phorbol effect. Our data suggest that activation of the PKC system might acutely limit the macrophage's ability to respond to C5a; chronically, phorbols upregulate receptor expression, most likely through positive effects on C5aR gene expression.