bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rabbit vascular endothelial adhesion molecules: ELAM-1 is most elevated in acute inflammation, whereas VCAM-1 and ICAM-1 predominate in chronic inflammation
Authors: Abe Yasuharu , Sugisaki Katsunori , Dannenberg Arthur M 
Published: January 2018

Abstract
Activation of the microvasculature is a major component of the inflammatory response. During inflammation the vascular endothelium not only becomes more permeable to plasma proteins but also develops adhesion molecules that initiate the local immigration of leukocytes. We describe herein the in vivo changes in the three major vascular adhesion molecules during the development and healing of two types of rabbit dermal inflammatory lesions: (1) acute lesions produced in rabbits by the topical application of 1% sulfur mustard (SM, the military irritant/toxicant); and (2) chronic (immune-mediated) lesions produced in rabbits by intradermal injections of Mycobacterium bovis (BCG), the vaccine strain of tubercle bacillus. In each case, frozen tissue sections were made from lesions of various ages and stained immunohistochemically for von Willebrand (vW) factor to measure the total functional microvasculature. The sections were also stained immunohistochemically for the vascular endothelial adhesion molecules ICAM-1, ELAM-1 (E-selectin), and VCAM-1, and for the leukocyte ligands for ICAM-1: LFA-1 (CDlla/CD18) and Mac-1 (CD11b/CD18). Infiltrating monocytes and lymphocytes expressed the LFA-1 ligand and infiltrating PMN expressed the MAC-1 ligand. The area of stained microvasculature per square millimeter of tissue section was determined with the use of a computerized image analyzer. Edema and cell infiltration spread apart the microvessels, changing the number of microvessels per square millimeter of tissue section. Three methods of assessing such changes are presented. In SM lesions, endothelial ICAM levels were decreased from normal by about 50% at 1 and 2 days (when the lesions reached their peak size) and returned to normal at 3 and 6 days (during the healing process). ELAM rose in peak SM lesions and remained high during healing. VCAM levels, however, were only elevated in the 6-day (almost healed) lesions. In BCG lesions the levels of endothelial ICAM and VCAM (and to a lesser extent ELAM) were increased at 9 days and remained so as the size of the lesions peaked at 23 days. During the healing phase at 37 days, the elevated ICAM and VCAM levels decreased but the slightly increased ELAM levels persisted. These findings indicate that ELAM plays a major role in acute inflammation and that VCAM and ICAM play major roles in chronic inflammation. VCAM is known to be monocyte and lymphocyte selective.
Cytotoxicity of peritoneal murine macrophages against encapsulated pancreatic rat islets: in vivo and in vitro studies
Authors: Kessler Laurence , Jesser Cathy , Lombard Yves , Karsten Véronique , Belcourt Alain , Pinget Michel , Poindron Philippe 
Published: January 2018

Abstract
The aim of this work was to study in vivo and in vitro the involvement of macrophages and interleukin-1β (IL-lβ) in the necrosis of encapsulated islets during xenograft and to evaluate the immuno-protective efficiency of the AN69 membrane. In vivo, 6 days after implantation, 65% of the membrane surface of the devices containing the islets was colonized with macrophages compared with only 5% of the surface of the empty control devices. The morphological aspect of implanted islets was altered and their insulin release decreased significantly compared with freshly isolated ones (265 ± 50 vs. 507 ± 81 μU/mL). In vitro, the insulin release of encapsulated islets cultured for 2 days decreased to 32 and 28%, respectively, in the presence of IL-1β and macrophages. The addition of anti-IL-1β antibody to the co-culture of macrophages and islets did not modify this loss of functional activity. Furthermore, IL-1β passed through the AN69 membrane. In conclusion, macrophages are involved in damaging encapsulated pancreatic islets and are probably partly responsible for islet transplantation failure.
Selective induction of peripheral and mucosal endothelial cell addressins with peripheral lymph nodes and Peyer's patch cell-conditioned media
Authors: Denis Véronique , Dupuis Philippe , Bizouarne Nadine , Sampaio Silvia de O , Hong Li , Lebret Marilyne , Monsigny Michel , Nakache Maurice , Kieda Claudine 
Published: January 2018

Abstract
Vascular endothelial cell addressins play an important role in lymphocyte homing in secondary lymphoid organs and in chronic inflammatory areas. A SV40 large T antigen-immortalized cell line from peripheral lymph nodes, HECa10 [Bizouarne et al., 1993a], was used to characterize the location of addressing with regard to environmental factors and cytokines. For this purpose, two monoclonal antibodies, MECA 79 and MECA 367, specific for peripheral lymph node vascular addressin and for mucosal addressin (Peyer's patches), respectively, were bound to unstimulated HECa10 cells. Both mucosal and peripheral addressins were detected inside the cells and in cellular extracts of the resting cells. On the cell surface, both addressins could be evidenced on the same cells at a moderate level of expression. They partly mediate the EL4/EL4IL2 lymphoma cells9 adhesion to HECa10 cells. Supernatants of cultured peripheral lymph node or Peyers' patch cells induced expression of MECA 79 or MECA 367 antigens, respectively, on the surface of HECa10 cells. Interleukins, IL-7, IL-3, and IL-8, induced the cell-surface appearance of MECA 79 but not of MECA 367 antigen. Therefore, the same cell type synthesizes both antigens, but the expression of these antigens on the cell surface is independently regulated, thus uncovering a characteristic tissue type-specific as well as environment-sensitive properties of microvascular endothelial cells.
Inhibition and stimulation of LFA-1 and Mac-1 functions by antibodies against murine CD18. Evidence that the LFA-1 binding sites for ICAM-1, -2, and -3 are distinct
Authors: Driessens Mariëtte H E , van Hulten Paula , Zuurbier Astrid , La Rivière Geertje , Roos Ed 
Published: January 2018

Abstract
The murine CD18 monoclonal antibody (mAb) M18/2 was reported to inhibit lymphoma metastasis [Zahalka, M. A. et al. (1993) J. Immunol. 150, 4466]. To identify the pathways potentially blocked, we studied the effects of M18/2 compared with two new mAb against murine CD18, GAME-46, and -245. Whereas the GAME mAb blocked most Mac-l-mediated interactions, M18/2 had no effect, or even stimulated. The same was true for adhesion of LFA-1 to ICAM-1. To test effects on interactions with different ICAMs, we used L cells transfected with human IGAM-1, -2, and -3. As previously described, mouse LFA-1 does not bind to human ICAM-1 but we show here that mouse LFA-1 does bind to human ICAM-2 and -3. Again, the GAME mAb blocked completely, but M18/2 did not. These results indicate that the LFA-1 binding sites for ICAM-1 and ICAM-2 and-3, although in close vicinity, are distinct. Furthermore, effects of M18/2 on metastasis cannot be ascribed to blocking of any known β2-integrin activity.
Epinephrine attenuates down-regulation of monocyte tumor necrosis factor receptors during human endotoxemia
Authors: van der Poll Tom , Calvano Steve E , Kumar Ashwini , Coyle Susette M , Lowry Stephen F 
Published: January 2018

Abstract
Epinephrine inhibits lipopolysaccharide (LPS) -induced tumor necrosis factor (TNF) production by increasing intracellular cAMP concentrations. Because agents that increase cAMP levels can enhance TNF receptor expression in vitro, granulocyte and monocyte TNF receptors were determined by FACS analysis in 7 normal humans who were receiving a constant 24-h infusion of epinephrine (30 ng/kg/min), and in 15 normal subjects after intravenous injection of LPS (2 ng/kg), while they were receiving a continuous infusion of epinephrine started either 3 h (EPI-3) or 24 h (EPI-24) before LPS injection or an infusion of normal saline (LPS; n = 5 per group). Infusion of epinephrine per se did not influence TNF receptor expression. LPS induced a transient decrease in monocyte TNF receptors and a more sustained decrease in granulocyte TNF receptors (both P &lt; 0.05). EPI-3 partly prevented LPS-induced down-modulation of monocyte TNF receptors (P &lt; 0.05 vs. LPS only), but did not affect LPS-induced down-modulation of granulocyte TNF receptors. EPI-24 had no effect on TNF receptor expression. These data suggest that epinephrine not only influences the bioavailability of TNF by an effect on the production of this proinflammatory cytokine, but also by modulating the expression of its receptors.
CD18 adhesion blockade decreases bacterial clearance and neutrophil recruitment after intrapulmonary E. coli, but not after S. aureus
Authors: Ramamoorthy Chandra , Sasaki Steve S , Su Daniel L , Sharar Sam R , Harlan John M , Winn Robert K 
Published: January 2018

Abstract
Leukocyte emigration in the lung occurs by both CD18-dependent and -independent mechanisms that are stimulus specific. We examined the effect of CD18 blockade (mAb 60.3) on neutrophil (PMN) emigration into, and bacterial clearance from, the lung. After intravenous treatment with either mAb 60.3 or saline, rabbits were given an intralobar inoculation with 109 colony-forming units of either Staphylococcus aureus or Escherichia coli. Four hours after inoculation, lungs were lavaged to assess PMN emigration. CD18 blockade reduced PMN emigration to E. coli by 76% but only 45% to S. aureus. Experiments to determine bacterial recovery from the lungs at 4, 8, and 24 h after inoculation showed that CD18 blockade impaired the early (4 h) clearance of E. coli but not S. aureus. These findings suggest that PMN emigration to intrapulmonary S. aureus is largely CD18-independent. In contrast, intrapulmonary E. coli elicits CD18-mediated PMN emigration. CD18 blockade results in impaired clearance of E. coli but not S. aureus from the lung.
Differential phosphorylation of the β2 integrin CD11b/CD18 in the plasma and specific granule membranes of neutrophils
Authors: Buyon Jill P , Philips Mark R , Merrill Joan T , Slade Seth G , Leszczynska-Piziak Joanna , Abramson Steven B 
Published: January 2018

Abstract
Neutrophil aggregation is mediated by the β2 integrin CD11b/CD18, which has limited expression on the surface membrane of resting cells but is recruited from intracellular organelles after cell activation. We have previously found that CD11b/CD18 newly translocated to the plasma membrane does not contribute to adhesion but must be modified to be functional. Because neutrophil aggregation induced by phorbol myristate acetate (PMA) is accompanied by de novo phosphorylation of the CD18 cytoplasmic tail, we sought to determine whether CD11b/CD18 phosphorylation is separately regulated in the different cellular compartments. Accordingly, [32P]-labeled CD11b/CD18 was immunoprecipitated from purified neutrophil-specific granule or plasma membrane lysates. In plasma membrane fractions, as in whole cell lysates, CD18 became phosphorylated in cells exposed to PMA but not in untreated cells or cells treated with N-formyl-methionyl-leucyl-phenylalanine (fMLP). The a chain, CD11h, was phosphorylated under all conditions. In contrast, only marginal phosphorylation of specific granule-associated CD18 or CD11b was observed. Calyculin A, an inhibitor of serine/threonine phosphatases (ppl &gt; pp2a), induced strong phosphorylation of CD18 in the plasma membrane but not in the specific granules. Addition of intact specific granule membranes to the plasma membranes from PMA-treated neutrophils markedly decreased phosphorylation in both CD11b and CD18 subunits. These data suggest that the phosphorylation of CD11b/CD18, which accompanies neutrophil activation, is limited to plasma membrane-associated molecules. Phosphorylation, either constitutive or induced, is absent in the specific granule membranes. The difference may be due to a specific granule-associated phosphatase, probably distinct from ppl. Therefore adhesion-competent plasma membrane CD11b/CD18 and adhesion-incompetent specific granule CD11b/CD18 differ in their state of phosphorylation.
Undifferentiated U937 cells transfected with chemoattractant receptors: a model system to investigate chemotactic mechanisms and receptor structure/function relationships
Authors: Kew Richard R , Peng Tina , DiMartino Stephen J , Madhavan Deepa , Weinman Shana J , Cheng Daniel , Prossnitz Eric R 
Published: January 2018

Abstract
Transfection of either the C5a receptor or the formyl peptide receptor into undifferentiated U937 cells generated continuously growing cell lines that stably expressed these receptors. The transfected cells displayed significant numbers of cell surface receptors that had ligand binding properties similar to fully differentiated U937 cells. Undifferentiated transfected U937 cells were capable of a ligand-specific calcium flux and showed migratory responses that were qualitatively and quantitatively similar to differentiated cells and were specific for each chemoattractant. Moreover, the chemotactic response could be desensitized by preincubating the cells in a high concentration of ligand and could be blocked by pertussis toxin. These results demonstrate that undifferentiated U937 cells possess the subcellular signaling apparatus and machinery necessary to generate a motile response and that the only missing component for chemotaxis is expression of a chemoattractant receptor. In addition, the results demonstrate that undifferentiated U937 cells transfected with chemoattractant receptors provide a defined model system to study receptor structure/function relationships and may be used to investigate receptor-mediated chemotactic responses in a relevant human myeloid cell.
MCP-1-mediated chemotaxis requires activation of non-overlapping signal transduction pathways
Authors: Yen Hua-hsing , Zhang Yujun , Penfold Sonya , Rollins Barrett J 
Published: January 2018

Abstract
Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that attracts monocytes and T lymphocytes. Its receptor (CCR2) is a heptahelical G-protein-coupled receptor (GPCR) whose signal transduction pathways for chemotaxis have not been completely defined. Because other GPCRs stimulate the mitogen-activated protein kinase (MAPK) cascade, we examined this pathway's activity in response to MCP-1. MCP-1 induced rapid and transient activation of MAPK in human monocytes and in Chinese hamster ovary cells expressing CCR2B. This effect was largely insensitive to pertussis toxin and wortmannin, and was protein kinase C-dependent and protein tyrosine kinase-independent. PD 098059, an inhibitor of MEK activation, not only prevented MAPK activation but also inhibited MCP-1-induced chemotaxis. Because pertussis toxin and wortmannin also efficiently inhibit chemotaxis but do not completely inhibit MAPK activation, these data may define non-overlapping signal transduction pathways that all must be activated to produce chemokine-mediated chemotaxis.
Development of laboratory and animal model systems for HIV-1 encephalitis and its associated dementia
Authors: Persidsky Yuri , Gendelman Howard E 
Published: January 2018

Abstract
The neuropathogenesis of HIV-1 encephalitis and its associated dementia revolves around sustained viral replication in cells of mononuclear phagocyte origin (brain macrophages, multinucleated giant cells, and microglia). Macrophage secretory factors play important roles in facilitating monocyte trafficking into the brain, in regulating productive viral replication, and in producing neurotoxic responses. To study these events, we constructed an artificial blood-brain barrier (BBB) to assay monocyte transendothelial migration and developed an animal model system for HIV-1 encephalitis to ascertain the role that virus-infected mononuclear phagocytes play in disease pathogenesis. The BBB model was composed of brain microvascular endothelial cells and astrocytes placed on opposite sides of a porous membrane. Monocyte activation, not HIV-1 infection per se, was the central event affecting monocyte BBB migration. Many of the pathological features of HIV-1 encephalitis were reproduced in SCID mice stereotactically inoculated with virus-infected monocytes. These included widespread astrogliosis, apoptosis of neurons, dendritic damage, and macrophage/microglial activation. Such laboratory and animal model systems are being used to ascertain the pathogenic potential of virus-infected macrophages in brain and ways to curb such injurious effects.
Possible participation of polymorphonuclear cells stimulated by microbial immunomodulators in the dysregulated cytokine patterns of AIDS patients
Authors: Cassone Antonio , Chiani Paola , Quinti Isabella , Torosantucci A 
Published: January 2018

Abstract
Macrophages and polymorphonuclear cells (PMN) play a major role as cells primarily responsive to microbial biological response modifiers (BRM). Although much attention has been given to macrophages, PMN have been relatively underinvestigated. We have recently studied the responses of PMN from HIV– and HIV+ subjects after stimulation with a powerful immunomodulatory fraction from the cell wall of Candida albicans (MP-F2) and compared this to bacterial lipopolysaccharide (LPS). Both cytokine patterns and PMN anticandidal activity were investigated. MP-F2, like LPS, was an active inducer of interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), IL-6, and IL-1β production by PMN and monocytes from all subjects. IL-12 was also produced by MP-F2-stimulated PMN in the presence of interferon-γ (IFN-γ). PMN from HIV+ subjects showed increased in vitro expression of TNF-α and IL-6 genes as determined by semiquantitative reverse transcriptase-polymerase chain reaction. In all subjects, cytokine gene expression was strongly stimulated by MP-F2 or LPS and inhibited by IL-10. Production of IL-6 and TNF-α protein (measured by ELISA) was higher in PMN from HIV+ subjects in at least one of the conditions tested (unstimulated or stimulated by LPS or MP-F2). However, the amount of the C-X-C chemokine IL-8 was equal in PMN from HIV– and HIV+ subjects. PMN from HIV+ subjects were at least as active in inhibiting candide growth as PMN from HIV– controls. In both groups PMN were equally stimulated by MP-F2 and LPS. Only in severely neutropenic subjects was there some reduction in the anticandidal activity but not in cytokine responses. When appropriately stimulated by microbial BRM, PMN are active producers of proinflammatory and immunomodulatory cytokines. This production is not only totally preserved in HIV+ subjects but may be higher than in PMN from HIV– subjects and may be coupled with an efficient anticandida activity. We suggest that during common bacterial or fungal infections PMN may contribute to the dysregulated production of inflammatory cytokines in AIDS patients.
Immune stimulation and HIV-1 viral replication
Authors: Wahl Sharon M , Orenstein Jan M 
Published: January 2018

Abstract
A biphasic early and late viremia is characteristic of HIV-1 infection. The first increase in circulating viral burden occurs within weeks after infection, before a host immune response, and the second, later peak emerges during the inevitable HIV-1 devastation of immune function. Recently, intermittent bouts of viremia have also been identified in HIV-1-infected individuals and found to be associated with episodes of immune challenge. Vaccinations, exposure to antigens, and infections often induce reversible increases in circulating viral levels, dependent on CD4+ T lymphocyte numbers. However, even with marked losses in CD4+ T cell counts, opportunistic infections appear to trigger a viremic response. In searching for the source of this virus, macrophages in tissues co-infected with opportunistic pathogens have been identified as prodigious producers of HIV-1. Thus, the fountain from which HIV-1 emerges may shift from CD4+ T lymphocytes in early HIV-1 infection to tissue macrophages later in the natural evolution of the disease, as the CD4+ T cells are depleted. Defining the mechanisms of this transitional event in HIV-1 infection may facilitate regulation and therapeutic control of both opportunistic infections and HIV-1.
Dexamethasone inhibits leukocyte emigration in rat mesenteric post-capillary venules: an intravital microscopy study
Authors: Tailor Anitaben , Flower Roderick J , Perretti Mauro 
Published: January 2018

Abstract
The effect of subcutaneous administration of dexamethasone (DEX) on interleukin-lβ (IL-lβ, 20 ng i.p., – 2 h) and platelet-activating factor (PAF, 100 nM in superfusion) -induced leukocyte interaction with the endothelium of rat mesenteric post-capillary venules was studied. DEX produced a dose-dependent inhibition of IL-lβ-induced leukocyte extravasation in the rat mesenteric vascular bed, with a calculated ED50 of 40 μg/kg and a maximal effect of 80–100% inhibition at 0.1 mg/kg. IL-lβ-induced cell adhesion to post-capillary venules was only partially inhibited by the steroid, with a calculated ED50 of 480 μg/kg and a maximal effect of 40–60% inhibition. Furthermore, the steroid inhibited leukocyte emigration, but not adhesion, caused by superfusion of the mesenteric vascular bed with PAF. A doubling of leukocyte emigration time (from 226 to 552 s) was observed after treatment of rats with DEX. Administration for 5 days of a dose of 10 μg/kg DEX (which was inactive when given as a single injection) resulted again in a selective inhibition of IL-lβ-induced leukocyte emigration, without effect on cell adhesion. These data demonstrate a preferential susceptibility of the leukocyte emigration process to the inhibitory action of DEX.
Regulation of cytosolic free Ca2+ in cultured rat alveolar macrophages (NR8383)
Authors: Zhang Guo H , Helmke Ronald J , Mörk Ann-Christin , Martinez J Ricardo 
Published: January 2018

Abstract
Ca2+ mobilization in the rat alveolar macrophage cell line NR8383 was examined with the Ca2+-sensitive fluorescent probe Fura-2. ATP and norepinephrine elicited a 108 and 46% increase, respectively, in cytosolic free Ca2+ concentration ([Ca2+]i). Acetylcholine, nicotine, isoproterenol, substance P, and vasoactive intestinal polypeptide did not alter [Ca2+]i. Inositol 1,4,5-trisphosphate (IP3) formation was also activated by ATP. The carbohydraterich cell wall preparation, zymosan, induced a gradual [Ca2+]i increase only in the presence of external Ca2+, but did not activate IP3 formation. This increase was abolished by laminarin and by removal of extracellular Ca2+, suggesting that the [Ca2+]i increase was activated by β-glucan receptors and mediated by Ca2+ influx. This influx was significantly reduced by SKF96365, but not by nifedipine, ω-conotoxin GVIA, ω-agatoxin IVA, or flunarizine. These results suggest that release of intracellular Ca2+ in NR8383 cells is regulated by P2-purinoceptors and that zymosan causes Ca2+ influx via a receptor-operated pathway.