bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intercellular adhesion molecule 1 (ICAM-1) expression and its role in neutrophil-induced ischemia-reperfusion injury in rat liver
Authors: Farhood Anwar , McGuire Gerald M , Manning Anthony M , Miyasaka Masayuki , Smith C Wayne , Jaeschke Hartmut 
Published: January 2018

Abstract
The potential role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of reperfusion injury was investigated in male Fischer rats subjected to 45 min of hepatic ischemia and 24 h of reperfusion. ICAM-1 mRNA levels increased during ischemia in the ischemic liver lobes; however, during reperfusion mRNA levels increased in both the ischemic and nonischemic lobes. Immunohistochemical evaluation indicated ICAM-1 expression only on sinusoidal lining cells in controls; ischemia-reperfusion enhanced ICAM-1 expression in the sinusoids and induced some expression on hepatocytes. The monoclonal anti–ICAM-1 antibody 1A29, but not an immunoglobulin G control antibody, administered at 1 h and 8 h of reperfusion (2 mg/kg) significantly attenuated liver injury as indicated by 51% lower plasma alanine aminotransferase activities and 32–36% less hepatic necrosis at 24 h without affecting reactive oxygen formation by Kupffer cells and hepatic neutrophils. Although 1A29 reduced neutrophil extravasation in a glycogen peritonitis by 60%, the antibody had no significant effect on hepatic neutrophil infiltration during reperfusion. These data suggest that ICAM-1 plays a significant role during the neutrophil-dependent injury phase after hepatic ischemia and reperfusion and therefore blocking this adhesion molecule may have therapeutic potential against postischemic acute liver failure. J. Leukoc. Biol. 57: 368–374; 1995.
Mature polymorphonuclear leukocytes express high-affinity receptors for IgG (FcγRI) after stimulation with granulocyte colony-stimulating factor (G-CSF)
Authors: Gericke Germo H , Ericson Solveig G , Pan Luying , Mills Letha E , Guyre Paul M , Ely Pamela 
Published: January 2018

Abstract
The high-affinity receptor for the constant region of immunoglobulin G IgG (FcγRI; CD64) is virtually undetectable on mature polymorphonuclear neutrophils (PMNs) in healthy individuals but is expressed on PMNs in patients with certain infections and in patients treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF). The induction of FcγRI by rhG-CSF has previously been reported to result from effects on immature granulocyte progenitors. To evaluate the G-CSF effect on mature PMNs, we studied the correlation between G-CSF plasma concentration and expression of FcγRI on PMNs in vivo as well as the effect of G-CSF on FcγRI expression on mature PMNs in vitro. FcγRI expression on PMNs correlated (R = 0.79; p &lt; .001) with plasma concentrations of endogenous or recombinant G-CSF in healthy volunteers and in patients undergoing high-dose chemotherapy and autologous bone marrow transplantation. PMNs exhibited a unimodal distribution for elevated FcγRI expression, suggesting that G-CSF induced increased expression of FcγRI on mature as well as on immature PMNs. In vitro, incubation of mature PMNs with G-CSF induced mRNA for FcγRI. Significant FcγRI surface expression was induced in a time- and dose-dependent manner. Thus, G-CSF can act on mature PMNs to increase FcγRI expression and may be useful for stimulating antibody mediated immune functions of PMNs in vivo. J. Leukoc. Biol. 57: 455–461; 1995.
The role of PECAM-1 (CD31) in leukocyte emigration: studies in vitro and in vivo
Authors: Muller William A 
Published: January 2018

Abstract
Platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a molecule capable of mediating both homophilic and heterophilic adhesion. It is constitu tively expressed and concentrated in the lateral borders between endothelial cells and expressed on the surfaces of neutrophils, monocytes, and some T cell subsets, as well as on platelets. In a quantitative in vitro assay, monoclonal antibody against PECAM-1 or soluble recombinant PECAM-1 selectively blocked passage of both neutrophils and monocytes across the endothelial monolayer by 70–90% without interfering with the ability of these cells to bind to the apical endothelial cell surface. These rea gents worked whether directed against leukocyte PECAM-1 or against endothelial cell PECAM-1 and were not additive, suggesting that a homophilic interaction was occurring. In a murine model of acute inflammation, thioglycollate-induced peritonitis, a monoclonal anti body against mouse PECAM-1 blocked emigration of leu kocytes into the peritoneal cavity down to background levels. Examination of peritoneal venules in these mice revealed many leukocytes in apparent contact with the endothelial surface but unable to cross the intima. Thus, PECAM-1 has a distinct role in the transendothelial migration phase of leukocyte emigration, independent of the adhesion events on the apical surface. J. Leukoc. Biol. 57: 523–528; 1995.
Localization of cyclic GMP-dependent protein kinase in human mononuclear phagocytes
Authors: Pryzwansky Katherine B , Kidao Sudha , Wyatt Todd A , Reed William , Lincoln Thomas M 
Published: January 2018

Abstract
The presence and physiological role of cGMP-dependent protein kinase (G-kinase) was investigated in human mononuclear phagocytes. Western blots of mono cyte extracts revealed a single polypeptide band that comigrated with purified bovine lung G-kinase. G-kinase was localized by immunofluorescence microscopy in freshly isolated adherent human monocytes, monocyte-derived macrophages cultured from 4 to 14 days, and al veolar macrophages. In monocytes, G-kinase was local ized in granules or vesicles in the cytoplasm, at the microtubule organizing center, on filaments, and in the nucleus. In monocyte-derived macrophages, intense staining for G-kinase was found in the vicinity of the Golgi, in vesicles throughout the cytoplasm, and diffusely in the nucleus. Dual-label confocal laser scanning microscopy demonstrated that G-kinase was colocalized with the endoplasmic reticulum. For comparison, G-kinase was localized in alveolar macrophages that were adhered from 3 to 30 min. In these cells, G-kinase was prominent within the organelle-rich area pericortical to the nucleus. However, a well-defined area of intense staining was also observed at the cell periphery at early time points during adherence and spreading. Rhodamine-labeled phalloidin showed that this peripheral area was rich in F-actin. Cytochalasin D, but not nocodazole, in hibited G-kinase targeting to the cell margin. Further more, the guanylate cyclase inhibitor LY83583 inhibited alveolar macrophage spreading and staining for G-kinase at the cell periphery. These data suggest that G-kinase may play an important role in cGMP-mediated regulation involved in protein processing and cell motility. J. Leukoc. Biol. 57: 670–678; 1995.
Priming of tyrosine phosphorylation in GM-CSF-stimulated adherent neutrophils
Authors: Johnson George M , Gomez-Cambronero Julian 
Published: January 2018

Abstract
Adherence of human neutrophils to plastic, fibronectin, or collagen-coated surfaces modifies their response to several agonists including granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor α (TNF-α), and fMet-Leu-Phe, permitting them to trigger superoxide anion (O2-) release, which they are unable to do as cells in suspension. Adherence of neu trophils causes a slight decrease in the basal level of tyro sine phosphorylation compared with that of suspended cells. The addition of GM-CSF, however, brings all pro teins to a level of phosphorylation at least equal to that seen in suspended cells. In the case of a 130-kDa (pl30) and a 42-kDa (p42) protein, the increase in tyrosyl phos phorylation in response to GM-CSF challenge is clearly larger in adherent than in suspended cells (6- and 4-fold increases for p130 and p42, respectively, in adherent cells vs. 1.7- and 2.1-fold in suspended cells). This is even more patent in the case of collagen-coated plates (9.4-fold in crease for p42). Therefore, once neutrophils attach to sur faces, they become primed and respond to GM-CSF with greater potency than when they are in suspension. By Western blot analysis with anti-MAP kinase antibodies, we demonstrate that p42 is one member of the mitogenactivating protein kinase, namely the p42MAPK. The tyrosyl phosphorylation of p42MAPK is elevated in GM-CSF-treated adherent neutrophils in a time-dependent fashion as measured by the formation of a doublet com posed of the phospho (or activated) form and the dephospho (or inactive) form of MAP kinase. MAP kinase activation and tyrosine phosphorylation are in hibited by tyrosine kinase inhibitors genistein and tyrphostin-23. Our results indicate that adherence acts to prime neutrophils for enhanced functionality and that tyrosine phosphorylation is involved in this process. J. Leukoc. Biol. 57: 692–698; 1995.
Dietary modulation of Kupffer cell and splenocyte function during a Salmonella typhimurium challenge in mice
Authors: Eicher Susan D , McVey D Scott 
Published: January 2018

Abstract
Oils from cold-water fish are rich in (n-3) polyunsaturated fatty acids, in particular eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6). Although those fatty acids are beneficial in the prevention of carliac disease and have anti-inflammatory properties, they can also decrease survival rates of mice during challenges with food-borne pathogens. This study was designed to determine dietary fat effects on Kupffer cells and splenocytes during a Salmonella typhimurium challenge. Mice were fed a low corn oil diet (3%, control), high corn oil diet (20%, HCO), or a menhaden fish oil diet (17% + 3% corn oil, FO) for 28 days and then orally given 3.1 108 colony-forming units of S. typhimurium. Kupffer cells and splenocytes were separated immediately prior to and on days 6, 10, and 14 postchallenge. Fish oil decreased Kupffer cell phagocytosis and oxidative burst early in the infection and adhesion molecule (CD 18) expression at the end of the infection. In splenocytes, fish oil affected la expression prior to and late in the infection and depressed CD18 expression late in the infection. These data suggest that the diet affected Kupffer cells most early in the infection but affected splenocytes primarily later in the infection. Therefore, because the greatest death rate during an S. typhimurium infection occurs early, the reduced function of the Kupffer cells is probably a major factor. J. Leukoc. Biol. 58: 32–39; 1995.
Graded changes in the response of individual human basophils to stimulation: distributional behavior of events temporally coincident with degranulation
Authors: MacGlashan Donald W 
Published: January 2018

Abstract
Human basophils, stimulated with either anti-IgE antibody or formyl-methionine-leucine-phenylalanine, were examined by two measures of the cell response that may reflect degranulation. Flow cytometric measurement of either of these two measures, changes in forward scatter intensity (an indirect measure of the basophil size) or changes in the intensity of acridine orange-loaded cells (which labels basophil granules), allowed an assessment of the distribution of single cell responses. With regard to the latter technique, structures that appeared to be basophil granules were shown to metachromatically label with low concentrations of acridine orange, which has little or no effect on histamine release. During stimulation these labeled granules were lost, leading to decreased fluorescence. Changes in either the forward scatter parameter or acridine orange labeling occurred on the same time scale as histamine release, differentiating these measures of the basophil response from early signal transduction events. Challenging basophils with a combination of phorbol myristate acetate and ionomycin caused 100% histamine release and allowed a measurement of the maximum change in forward scatter intensity or loss of acridine orange labeling. The flow cytometric distributions after this treatment were then compared with the distributions obtained by challenging cells with several concentrations of anti-IgE antibody or formyl-methionine-leucine-phenyialanine, which induced various submaximal responses. These flow cytometric distributions demonstrated that single cells could be found in intermediate states of activation, i.e., the response of all cells was graded according to the strength of the stimulus. These studies lead to the general conclusion that all aspects of the basophil response, including those late events in the basophil response we have studied here, as well as early events that we have studied previously, are graded in a continuous manner, according to the magnitude of the stimulus. J. Leukoc. Biol. 58: 177–188; 1995.
Role of interferon-γ in immune cell regulation
Authors: Young Howard A , Hardy Kenneth J 
Published: January 2018

Abstract
In 1965 Wheelock reported that phytohemagglutinin could induce from human leukocytes an interferon-like virus inhibitor [1]. This substance, which turned out to be interferon-γ (IFN-γ), has been the subject, directly or indirectly, of thousands of scientific publications since that initial report. Past research has led to the general conclusion that IFN-γ is much more than an interferon in that it has broader effects on the various arms of the immune system than most any other lymphokine or cytokine. In this review we discuss the effects of IFN-γ on the various cell lineages of the immune system, focusing on the biology of its actions. In addition, we summarize research focused on the consequences of introducing IFN-γ cDNA into tumor cells, aberrant IFN-γ production in transgenic animals, and inhibition of IFN-γ effects by knocking out either the IFN-γ gene itself or the IFN-γ receptor gene.
Colony-stimulating factor-1 expression in the human fetus and newborn
Authors: Roth Philip , Stanley E Richard 
Published: January 2018

Abstract
Colony-stimulating factor-1 (CSF-1) is a hematopoietic growth factor that regulates the survival, proliferation, and differentiation of mononuclear phagocytes. Because this cellular compartment undergoes major changes during fetal and neonatal life, we examined concurrent CSF-1 expression during human development. While levels increased dramatically after full-term birth, CSF-1 concentrations steadily declined in the preterm circulation from 2.7 to 1.9 times adult values as gestational age increased. CSF-1 was already detectable at 10 weeks gestation in spleen, intestine, lung, kidney, heart, and liver in order of decreasing concentration, but a positive correlation with gestational age was seen only in lung and intestine. Although a 4.4-kb CSF-1 mRNA was detectable in all tissues at all gestational ages, increased expression with advancing gestational age was observed in lung and kidney, whereas a rise and fall was observed in spleen. We conclude that CSF-1 concentration in the human circulation is developmentally regulated and that its expression in fetal tissues is compatible with its role in regulating the development of tissue mononuclear phagocytes.
Protein kinase C and intracellular pH regulate zymosan-induced lysosomal enzyme secretion in macrophages
Authors: Tapper Hans , Sundler Roger 
Published: January 2018

Abstract
Binding of zymosan particles to macrophage β-glucan receptors has previously been shown to trigger exocytosis of preformed lysosomal contents. In the present study, the involvement of Ca2+-, PKC-, and pH-dependent processes in the signaling to macrophage lysosomal secretion by zymosan was investigated. Also, the PKC dependence of lysosomal secretion in response to some soluble agents that directly alters intracellular pH was considered. Signaling to macrophage lysosomal secretion differs from that of many other secretory systems, because an elevation of cytosolic Ca2+ did not trigger a large secretory response, nor did attempts to reduce cytosolic Ca2+ affect the lysosomal secretory response to other stimuli. PKC activation by phorbol diester was also a poor stimulus of lysosomal secretion. However, when triggered by zymosan or by soluble stimuli raising lysosomal pH, the secretory response could be down-regulated by a prior prolonged incubation with phorbol diester. Such treatment also had marked effects on the binding and uptake of zymosan particles, the study of which was made possible by a novel approach. Furthermore, a synergistic effect on lysosomal secretion was obtained when stimuli that elevated lysosomal pH and stimuli that activated PKC were combined. This is of likely relevance for the secretory response to zymosan particles, a stimulus that both activates PKC and elevates lysosomal pH. The secretory response to zymosan was furthermore shown to be inhibited by a reduction of extracellular pH or [Na+], conditions that impair macrophage extrusion of acid equivalents. Earlier studies using soluble stimuli have shown a sensitivity of the secretory response to changes in cytosolic pH. We suggest a model in which the lysosomal secretory response to an elevation of lysosomal pH (1) is dependent on basal PKC activity and (2) can be enhanced further by activation of PKC. We consider PKC activity and elevation of lysosomal pH as independent and necessary signals, while cytosolic pH has a modulatory effect on some component(s) in the signal transduction pathway or in the secretory apparatus itself.
The vesiculo-vacuolar organelle (VVO): a distinct endothelial cell structure that provides a transcellular pathway for macromolecular extravasation
Authors: Dvorak A M , Kohn Sarah , Morgan Ellen S , Fox Patricia , Nagy Janice A , Dvorak Harold F 
Published: January 2018

Abstract
The vesiculo-vacuolar organelle (VVO) is a recently described organelle found in the cytoplasm of endothelial cells that line tumor microvessels and normal venules. VVOs are grape-like clusters of interconnecting uncoated vesicles and vacuoles, bounded by trilaminar unit membranes, that span the entire thickness of vascular endothelium, thereby providing a potential transendothelial connection between the vascular lumen and the extravascular space. Macromolecular tracers preferentially cross hyperpermeable tumor microvessels through VVOs. The present investigation was undertaken to elucidate further the ultrastructure and function of VVOs in a murine ovarian carcinoma (MOT) and in normal venules. Morphometry revealed that VVOs were enormous cytoplasmic structures (median area, 0.12–0.14 μm2 in single electron micrographs). Moreover, the individual vesicles and vacuoles that comprised VVOs were on average substantially larger than capillary caveolae and followed a non-normal distribution that was skewed to the right. Specimen tilting provided conclusive evidence that individual VVO vesicles and vacuoles communicated with each other and with the endothelial cells’ plasma membranes by stomata, some of which were closed by diaphragms composed of a single membrane. Studies with two tracers, ferritin (FE, diameter ~ 11 nm) and horseradish peroxidase (HRP, diameter ~ 5 nm), revealed that passage of macromolecules through VVOs was regulated at the level of stomatal diaphragms, thereby demonstrating a mechanism for controlling the passage of macromolecules across endothelial cells. Thus, compared with tumor microvessels, little circulating FE and HRP entered the VVOs of normal venular endothelium because stomata joining vesicles and vacuoles to each other and to the lumen and ablumen were closed. VVOs and their component vesicles/vacuoles were readily distinguished from endosomal organelles such as coated vesicles and multivesicular bodies, which also accumulated FE and HRP. Our findings indicate that VVOs provide a major pathway for the extravasation of circulating macromolecules across endothelia taller than capillary endothelium and suggest that upregulated VVO function accounts for the well-known hyperpermeability of tumor blood vessels.
Regulation and expression of chemokines: potential role in glomerulonephritis
Authors: Brown Zarin , Robson Rachel L , Westwick John 
Published: January 2018

Abstract
Glomerular diseases represent the major cause of renal failure. Despite decades of research our understanding of the mechanism(s) associated with immune-mediated glomerular injury remains poor. Consequently most of the therapies that are used are nonspecific with major side effects and offer minimal therapeutic benefits for the patient. The need for new strategies for therapy is clear. The drawing of leukocytes from the circulation into the inflamed glomerulus, accompanied by proliferation of resident mesangial cells and expansion of the mesangial matrix are key processes in the pathogenesis of glomerulonephritis (GN). The migration of inflammatory cells into an extravascular site requires a series of coordinated signals including the generation of a chemotactic gradient by the cells of the extravascular compartment. The nature of the stimulus and the subsequent spectrum of chemotactic factors produced determine the specific leukocyte population recruited to the inflammatory site. Members of the chemokine family play a central role in this process by attracting and stimulating specific subsets of leukocytes. Our hypothesis is that mesangial cell-derived chemokines are responsible for the initiation and maintenance of glomerular inflammation; in this review we discuss our recent findings supporting this theory. Increasing our understanding of the intracellular pathways that regulate chemokine production in human mesangial cells may provide leads to the design of more effective therapies for the prevention and treatment of glomerular inflammation.
Development, differentiation, and phenotypic heterogeneity of murine tissue macrophages
Authors: Naito Makoto , Umeda Syuji , Yamamoto Takashi , Moriyama Hiroshi , Umezu Hajime , Hasegawa Go , Usuda Hiroyuki , Shultz Leonard D , Takahashi Kiyoshi 
Published: January 2018

Abstract
In murine ontogeny, macrophage precursor cells develop in the yolk sac and fetal liver. Primitive macrophages also appear in the yolk sac, migrate to various tissues, and differentiate into several fetal macrophage populations. Because the development of the monocytic cell lineage is incomplete in the early stage of fetal hematopoiesis, primitive/fetal macrophages are considered to originate from granulocyte-macrophage colony-forming cells or earlier macrophage precursors, bypassing the early monocytic cell series. In adult mice rendered severely monocytopenic by administration of strontium-89, resident macrophages are maintained by self-renewal. In contrast, administration of liposome-encapsulated dichloromethylene diphosphonate (clodronate) results in the elimination of various tissue macrophage populations. The repopulation of affected macrophages is dependent on the increase of precursors in the liver and spleen during the period of macrophage depletion. Such precursors reconstitute heterogeneous macrophage subpopulations. In mice homozygous for the osteopetrosis (op) mutation, the absence of macrophage colony-stimulating factor (M-CSF) activity results in a deficiency of monocytes and monocyte-derived macrophages. However, immature macrophages are present in various tissues. Administration of M-CSF to op/op mice induces the increased proliferative capacity and the morphological maturation of macrophages. However, the responses of individual tissue macrophage subpopulations to M-CSF are different. These results indicate that macrophage development, differentiation, and proliferation are regulated by the tissue microenvironment including the in situ production of macrophage growth factors in both fetal and adult life.