bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of Late Phase Enhanced Vascular Permeability in Rats by Selective Depletion of Neutrophils With a Monoclonal Antibody
Authors: Sekiya Sakae , Yamashita Takao , Sendo Fujiro 
Published: January 2018

Abstract
We investigated the role of neutrophils in increased vascular permeability by a selective reduction of neutrophils using a monoclonal antibody, RP-3. An intraperitoneal injection of RP-3 not only selectively depleted peripheral blood neutrophils, but prevented the neutrophil infiltration to the tissues. Proteose peptone, zymosan, and BCG induced three different types of inflammatory edema, showing the early phase only, early plus late phase, and the late phase only, respectively. Only the late phase response of zymosan and BCG was inhibited by a depletion of neutrophils by RP-3, though the early phase response induced by proteose peptone and zymosan was not affected. Reconstitution of neutrophil-depleted rats by in situ infection of these cells restored the inflammatory edema induced by BCG, depending upon the number of neutrophils injected.
Thiol Proteinase Inhibitors Reverse the Increased Protein Kinase C Down-Regulation and Concanavalin A Cap Formation in Polymorphonuclear Leukocytes From Chediak-Higashi Syndrome (Beige) Mouse
Authors: Sato Akihiko , Tanabe Fuminori , Ito Masahiko , Ishida Eiko , Shigeta Shiro 
Published: January 2018

Abstract
Protein kinase C (PKC) plays an essential role in intracellular signal transduction for various cell functions, including concanavalin A (Con A)-induced cap formation. This enzyme is known to be proteolysed by calpain, which is a Ca2+ -dependent thiol proteinase. As reported previously, in polymorphonuclear leukocytes (PMNs) from beige mouse, the model of Chediak-Higashi syndrome, Con A-induced cap formation significantly increased compared with that in normal mouse. However, after pretreatment of beige PMNs with the thiol proteinase inhibitors leupeptin or E-64, the capping decreased to normal levels. Meanwhile, Con A-induced the translocation of PKC from the cytosolic to membrane fraction within 5 min in both mice, which is essential to the activation of this enzyme. However, after the translocation, an abnormal rapid decline in membrane-bound PKC activity was noted in beige mouse PMNs. Both leupeptin and E-64 also corrected the rapid decline in PKC activity observed in the beige mouse. These findings suggest that the normalization of Con A cap formation in beige mouse PMNs by the thiol proteinase inhibitors is associated with the correction of abnormality in PKC activity.
Characterization of Macrophage Subsets Regulating Murine Natural Killer Cell Activity
Authors: Nelson John A S , Parhar Ranjit S , Scodras John M , Lala Peeyush K 
Published: January 2018

Abstract
We examined the relationship of l-A expression by normal murine macrophages to their immunoregulatory role on natural killer cell activity. Macrophages were isolated on the basis of plastic adherence; characterized on the basis of conventional markers such as phagocytic ability, cytoplasmic non-specific esterase activity, surface MAC-1 and F4/80 antigen expression; and then used for functional studies relative to their expression of surface l-A. Two functional macrophage subsets were identified: NK-stimulatory and NK-suppressive subsets. The former function was associated with splenic macrophages, which were predominantly l-A+ as identified with a radioautographic immunolabeling technique; the latter function with peritoneal macrophages which were predominantly l-A-. Loss of macrophage l-A expression in vitro was delayed in the presence of indomethacin and enhanced in the presence of PGE2, indicating that PGE2 down-regulates l-A expression on macrophages. The NK stimulatory function of l-A+ macrophages was attributable to a soluble mediator, identified as IFN-γ, since the stimulatory ability was abrogated with an anti-IFN-γ antibody. l-A expression appears to be important for the stimulatory function, since some interference with this function was noted in the presence of anti-I-A antibody. The NK-suppressor function of I-A- macrophages was attributable to the soluble mediator PGE2, since this function was abrogated with indomethacin or anti-PGE2 antibody. These results are relevant to the understanding of normal in vivo immunoregulation by macrophages.
Down-Regulation of Macrophage I-A Expression in Tumor-Bearing Mice
Authors: Nelson John A S , Parhar Ranjit S , Scodras John M , Lala Peeyush K 
Published: January 2018

Abstract
During the subcutaneous growth of a highly metastatic mammary adenocarcinoma line, C3-L4 in C3H/HeJ mice, there was a rapid decline in macrophage l-A expression in vivo. The incidence of l-A+ macrophage subset in the spleen declined from 90% to 10% or less within 5 days of tumor transplantation, with a parallel decline in their absolute number. l-A expression in these cells remained suppressed for a long time until tumors became necrotic and ulcerated. In spite of a low incidence (15–20%) of l-A+ macrophages in the normal peritoneal space, tumor transplantation caused a long-lasting decline in their incidence to one-fourth of the original level. Tumor-associated macrophages were predominantly l-A- throughout the tumor life span. Thus l-A- macrophages dominated in all anatomical compartments in tumor-bearing mice. Macrophage l-A expression was substantially restored (spleen) or stimulated (peritoneal space and tumor) in tumor-transplanted mice subjected to chronic indomethacin therapy in the drinking water, indicating a reversal of prostaglandin-mediated down-regulation of macrophage l-A expression in situ. Concomitantly, this therapy caused regression of the primary tumors and prevented lung metastasis. These results are relevant to the understanding of tumor–host interactions and its exploitation for immunotherapy.
High-Affinity Binding of Fibronectin to Cultured Kupffer Cells
Authors: Cardarelli Pina M , Blumenstock Frank A , McKeown-Longo Paula J , Saba Thomas M , Mazurkiewicz Joseph E , Dias James A 
Published: January 2018

Abstract
Hepatic Kupffer cells are a major component of the reticuloendothelial or macrophage system. They were the first phagocytic cell type whose phagocytosis was shown to be influenced by plasma fibronectin, a dimeric opsonic glycoprotein. In the current study, the binding of soluble radioiodinated fibronectin purified from rat serum to isolated rat hepatic Kupffer cells was investigated using a cultured Kupffer cell monolayer technique. Binding was specific, since unlabeled purified fibronectin competed in a dose-dependent manner with the 125I-fibronectin for binding to the Kupffer cells. Addition of gelatin enhanced the binding of 125I-fibronectin to Kupffer cells. The phagocytosis of gelatinizedcoated red cells by Kupffer cells was increased either by preopsonizing the target particles with purified fibronectin or by the addition of purified fibronectin to the culture medium. In contrast, exposure of the Kupffer cells to medium containing purified fibronectin followed by wash-removal of the fibronectin did not increase the uptake of gelatin-coated red blood cells, even though fibronectin was detected on the surface of the Kupffer cells by immunofluorescence. Trypsinized monolayers expressed decreased capacity to bind 125I-fibronectin as well as fibronectin-coated sheep erythrocytes. The binding of 125I-fibronectin-gelatin complexes was inhibited by excess unlabeled fibronectin. We calculated that specific high-affinity (Kd = 7.46 × 10-9 M) binding sites for fibronectin exist on Kupffer cells. There are approximately 2,800–3,500 binding sites or putative “fibronectin receptors” per Kupffer cell. These sites appear to mediate the enhanced phagocytosis of gelatin-coated particles opsonized by fibronectin.
Activated Neutrophils Induce Erythrocyte Immunoglobulin Binding and Membrane Protein Degradation
Authors: Weiss Douglas J , Murtaugh Michael P 
Published: January 2018

Abstract
Neutrophil-induced alterations in feline erythrocytes were investigated to elucidate the pathogenesis off the erythrocyte destruction associated with inflammatory disease. Incubation of erythrocytes with zymosan-activated neutrophils, at target:effector concentrations of 50:1, resulted in immunoglobulin binding to the erythrocyte membrane and degradation of membrane proteins. Vitamin E and superoxide dismutase/catalase attenuated the immunoglobulin binding. Proteolysis was not prevented by addition of antioxidants or protease inhibitors to the erythrocyte:neutrophil coculture and was not reproduced with chemical oxidation or calcium loading of erythrocytes.
Effect of Retinoids on the Release and Gene Expression of Tumor Necrosis Factor-α in Human Peripheral Blood Monocytes
Authors: Turpin Jim , Mehta Kapil , Blick Mark , Heater Jeane P , Lopez-Berestein Gabriel 
Published: January 2018

Abstract
The effect of retinoic acid (RA) and retinol (ROH) on the release of tumor necrosis factor (TNF) by human peripheral blood monocytes (HPBM) was determined. HPBM were cultured for various periods of time in either 5% complete (cAB) or delipidized (DLS) AB serum. TNF release (L929 cytolytic assay) in the presence of cAB occurred during the first 3 days of in vitro culture. Delipidization of AB serum completely inhibited the lipopolysaccharide (LPS)-induced release of TNF by HPBM. Addition of RA (0.5 μM) to DLS restored LPS-induced TNF release by HPBM, and supplementation with ROH (1.0 μM) resulted in release of TNF-like activity, but only after 3 days of in vitro culture. The maintenance of TNF release by the addition of exogenous RA after 3 days of in vitro culture suggested that depletion of endogenous RA was partially responsible for loss of TNF-like activity. The levels of endogenous TNF protein and mRNA were not influenced by delipidization of serum and were found to be similar to those of HPBM cultured in the presence of AB serum. TNF protein and mRNA were undetectable in HPBM ROH-treated cell lysates, although cytolytic activity was observed in culture supernatants. These results suggest that retinoids are required for the release of cytolytic factors from HPBM and that non-TNF cytolytic factors may be released by these cells at different stages of maturation.
Bleomycin Binding Sites on Alveolar Macrophages
Authors: Denholm Elizabeth M , Phan Sem H 
Published: January 2018

Abstract
Previous work has demonstrated that bleomycin can directly stimulate alveolar macrophage secretion of fibroblast growth factors and monocyte chemotactic factors. In this study, rat alveolar macrophages obtained by bronchoalveolar lavage were examined for the presence of bleomycin binding sites, which might mediate this response. The results indicated that alveolar macrophages have specific, saturable, and reversible binding sites. Both high- and low-affinity binding sites were found; each macrophage possessed 6.7 × 104 high-affinity sites, with a Kd, of 528 nM, and 2.2 × 106 low-affinity sites, with a Kd of 65 μM. The Kd of the high-affinity sites corresponds closely to the ED50 obtained from dose-response curves of the bleomycin-stimulated secretion of both fibroblast growth and monocyte chemotactic factors, suggesting that bleomycin stimulation of alveolar macrophage function responses may be mediated by bleomycin interaction with these sites.
Bacterial Lipopolysaccharide Induces Release of Tumor Necrosis Factor-α From Bovine Peripheral Blood Monocytes and Alveolar Macrophages In Vitro
Authors: Adams Jeffrey L , Czuprynski Charles J 
Published: January 2018

Abstract
In this study, we demonstrate that freshly adherent bovine monocytes release tumor necrosis factor-α (TNF-α) in response to stimulation with bacterial lipopolysaccharide (LPS). TNF-α was detected using actinomycin D-treated WEHI-164 murine fibrosarcoma cells as targets in an 18 hr cytotoxicity assay. Doses of LPS from 20 ng/ml to 20 μg/ml were capable of inducing bovine TNF-α. The kinetics of TNF-α release from bovine monocytes demonstrated peak levels of cytotoxic activity at 1–3 hr post-LPS treatment, with a subsequent decline to background levels by 18 hr post-LPS treatment. A monoclonal antibody that neutralizes recombinant human TNF-α (rHuTNF-α) significantly reduced the cytotoxicity of LPS-stimulated bovine monocyte culture supematants. Size exclusion high-performance liquid chromatography (HPLC) analysis of LPS-stimulated monocyte and alveolar macrophage culture supematants resulted in a molecular weight elution profile similar to that of recombinant human TNF-α. These elution profiles are consistent with the presence of multimers of TNF-α. This is believed to be the first report of the in vitro production of bovine TNF-α.
Modulation of Nitrogen Oxide Synthesis In Vivo: NG-Monomethyl-L-Arginine Inhibits Endotoxin-Induced Nitrate/Nitrate Biosynthesis While Promoting Hepatic Damage
Authors: Billiar T R , Curran R D , Harbrecht B G , Stuehr D J , Demetris A J , Simmons R L 
Published: January 2018

Abstract
Attempts were made to promote or inhibit nitric oxide (·N=O) synthesis in a murine model of hepatic damage (Corynebacterium parvum followed by lipopolysaccharide; LPS) to determine the role of N=O in the liver injury. Moderate hepatic damage and increases in circulating NO2-/NO3- levels were detectable after C. parvum alone. Administration of LPS to these mice resulted in severe hepatic damage and acute elevations in circulating nitrogen oxide levels. L-arg had no influence on the C. parvum or LPS-induced changes. NG-monomethyl-L-arginine (NMA) had no effect in the absence of LPS, but when given with LPS, a dose-dependent suppression in plasma NO2-/NO3- levels and an increase in liver injury were seen. The NMA-induced changes were partially reversed by the simultaneous administration of L-arg. These findings suggest a protective role for · N=O in this model.
Stimulus-Dependent Leukotriene Release From Human Basophils: A Comparative Study of C5a and Fmet-leu-phe
Authors: MacGlashan Donald , Warner Jane 
Published: January 2018

Abstract
Previous studies of human basophil mediator release have noted that the bacterial peptide fmet-leu-phe and the anaphylatoxin C5a induce comparable levels of histamine release while only fmet peptide induces leukotriene release. Since 5-lipoxygenase metabolism of arachidonic acid is calcium dependent, we examined the characteristics of the human basophil [Ca++]i response which follows its activation by either fmet peptide or C5a. While the peak [Ca++]i response was essentially identical for these two stimuli, fmet peptide induced a prolonged increase in [Ca++]i while C5a stimulated only a transient increase in [Ca++]i that was essentially over within 2 minutes of adding the stimulus. Simultaneous addition of EDTA with fmet peptide revealed the two phases of the [Ca++]i response and demonstrated that leukotriene release was dependent on an elevated [Ca++]i level in the 2–5 minutes following challenge. Enhancement of leukotriene release induced by C5a by agents such as staurosporine and interieukin-3 also produced a [Ca++]i kinetic curve which resembled fmet piptide. Single cell studies of the [Ca++]i response could detect no subpopulations of cells which responded preferentially to fmet peptide or C5a, eliminating the possibility that the ability of fmet peptide to induce leukotriene was a result of its action on a functionally distinct population of basophils.
Syngeneic B Lymphoma Cells Provide a Unique Stimulus to Natural Killer (NK) Cells in Genetically Low-NK SJL/J Mice
Authors: Lin Tao-Zhen , Ponzio Nicholas M 
Published: January 2018

Abstract
SJL/J mice are a genetically low-NK strain, and their cytotoxic activity cannot be augmented with conventional NK inducers. In contrast, effector cells taken from the lymphoid tissues of SJL mice bearing a syngeneic B cell lymphoma (RCS) show variable, but significant levels of cytotoxic activity against NK-susceptible targets, such as YAC-1. Previous results suggested that the RCS cells themselves contributed to this cytotoxicity. However, results presented here indicate that most, if not all of the activity present within the lymphoid tissues of RCS-bearing mice is mediated by RCS-activated, host NK cells. These results were confirmed by in vitro studies, which demonstrate that both gamma irradiated (γ-) RCS cells and γ-allogeneic spleen cells induce cytotoxic activity in SJL spleen cells against YAC targets. However, the cytotoxicity induced by γ-allogeneic cells is mediated largely by lymphokine-activated killer (LAK) cells, since these effectors also lyse NK-resistant target cells, such as L1210. In contrast, the cytotoxic effector cells that are induced by syngeneic γ-RCS cells cause lysis of YAC targets, but not L1210 target cells. These data indicate that the syngeneic B cell lymphomas of SJL mice are a unique stimulus for host NK cells in this strain. Since activated NK cells produce a variety of lymphokines, RCS stimulation of host NK cells in SJL mice may provide some of the growth-promoting lymphokines that are known to be necessary for progressive growth of these lymphoma cells.
Tumoricidal Activity of Alveolar and Peritoneal Macrophages of C57BL/6 Mice Bearing Metastatic or Nonmetastatic Variants of Lewis Lung Carcinoma
Authors: Duffie G Patrick , Young M Rita I 
Published: January 2018

Abstract
The spontaneous tumoricidal abilities of alveolar and peritoneal macrophages from C57B1/6 mice bearing a metastatic or a nonmetastatic cloned variant of Lewis lung carcinoma (LLC) were measured. Cytotoxicity by alveolar macrophages was enhanced during the first few weeks after subcutaneous (s.c.) or intravenous (i.v.) injection of metastatic LLC-C3 cells, but not after injection of nonmetastatic LLC-C8 cells. Alveolar macrophages from mice with s.c.-lnjected metastatic tumors, but not with nonmetastatic tumors, could be further activated in vitro, but not beyond the maximal level of spontaneous cytotoxicity. Late in tumor growth, the spontaneous cytotoxicity by alveolar macrophages of metastatic LLC-C3 tumor bearers was suppressed and could not be increased by in vitro activation. The tumoricidal abilities of peritoneal macrophages from mice bearing either LLC-C3 or LLC-C8 tumors were modulated in a similar way, as were alveolar macrophages. The reduced cytotoxicity by alveolar macrophages from mice with nonmetastatic tumors or from mice bearing large metastatic tumors was not due to suppression by macrophage-derived prostaglandins. The loss of tumoricidal capabilities by macrophages from mice with large metastatic LLC-C3 tumors was not caused by elevated systemic prostaglandin E2 (PGE2) levels. These results suggest that alveolar and peritoneal macrophages are activated to be cytotoxic during development of pulmonary metastases and do not need to be functionally depressed for successful establishment of metastases.
Monovalent Fab Fragments of D7.5 Monoclonal Antibody Activate Intracellular Ca2+ Mobilization and Secretion of Cytolytic Factors by Thymus Cells
Authors: Peacock James S , Tan Jacqueline , Guffee Judy , Stein-Streilein Joan 
Published: January 2018

Abstract
Previous studies have identified two mouse monoclonal antibodies, D7.5 and G1.4, that each can cause secretion of cytolytic factors from natural killer (NK) cells and resting T cells in humans, rats, and hamsters. Toward elucidation of the molecular identity and the transmembrane signaling mechanism of the antibody-defined trigger molecules, we investigated 1) their surface density, 2) the crosslinking requirement for signaling, and 3) their ability to mobilize intracellular calcium ions. Equilibrium binding studies using monovalent Fab fragments of D7.5 showed the presence of approximately 20,000 trigger molecules per thymus cell and an antibody dissociation constant of 1.8 x 10-6 M. Thymus cells incubated in the presence of either intact or Fab fragments of D7.5 acquired the ability to lyse Yac-1 cells. Furthermore, the incubation media of thymocytes that were treated with either intact or Fab fragments of D7.5 contained effector-cell derived factors that could lyse Yac-1 cells. Flow cytometry measurements of changes in intracellular free calcium concentration ([Ca2+]i) in thymocytes. A significantly elevated level of [Ca2+]i was observed at 60s after antibody addition and this response, which required the external calcium source, increased continuously during the 30 min incubation. Furthermore, dbcAMP plus theophylline did not alter the ability of D7.5 to induce calcium mobilization suggesting that the antibody-defined trigger may not use the signaling pathway involving breakdown of phosphatidylinositol.
Inhibition of Cluster Formation and Lymphocyte Proliferation by Anti-Fibronectin Antiserum
Authors: Klingemann H-G , Storb R , Deeg H J 
Published: January 2018

Abstract
Dendritic cells (DC) confer concanavalin A responsiveness to accessory cell-depleted canine lymphocytes. DC-lymphocyte cluster formation is followed by blast transformation and proliferation of lymphocytes. We investigated whether fibronectin, which is known to be involved in cell:cell interactions, might also be involved in the interaction between canine DC and lymphocytes. The addition of rabbit anti-dog fibronectin antiserum to concanavalin A-stimulated peripheral blood mononuclear cells decreased cluster formation and reduced 3H-thymidine incorporation by 57–70%. Similarly, when cell fractions, enriched for DC, were pretreated with anti-fibronectin antiserum before being added back to accessory cell-depleted lymphocytes, cluster formation was reduced and lymphocyte proliferation after concanavalin A stimulation decreased by 18–46% as measured by 3H-thymidine uptake. Ferritin-conjugated anti-fibronectin antibody was bound to the surface of DC, primarily at the dendritic processes. We conclude that fibronectin, located on the surface of canine DC, participates in the accessory cell function of these cells.
Monoclonal Antibodies to the Leukocyte Membrane CD18 Glycoprotein Complex and to Intercellular Adhesion Molecule-1 Inhibit Leukocyte-Endothelial Adhesion in Rabbits
Authors: Argenbright L W , Letts L G , Rothlein R 
Published: January 2018

Abstract
Increasing evidence indicates that leukocyte-endothelium adhesion is mediated, in part, by the CD11/CD18 family of heterodimeric glycoproteins expressed on the leukocyte plasma membrane and by intercellular adhesion molecule-1 (ICAM-1) which is expressed on endothelial cells. We have used the technique of intravital microscopy to visualize the microcirculation of the rabbit mesentery and to evaluate effects of antibodies against several adhesion glycoproteins on C5a-induced leukocyte adhesion. Addition of zymosan-activated serum (a source of C5a) to the buffer superfusing the mesenteric microvasculature induced rapid adhesion of leukocytes to the endothelium of post-capillary venules. Monoclonal antibodies R15.7 (anti-CD18), R7.1 (anti-CD11a, LFA-1), and R6.5 (anti-ICAM-1), administered intravenously before C5a exposure, strongly inhibited leukocyte adherence while antibody LM2 (anti-CD11b, Mac-1) produced significant, but weaker, inhibition. If these antibodies were administered after C5a-induced adhesion had begun, both R15.7 and R7.1 displaced adherent leukocytes and prevented further leukocyte accumulation: LM2 and R6.5 did not displace adherent leukocytes or inhibit incoming leukocytes from adhering. These data confirm earlier findings establishing a role for CD18 in leukocyte adhesion in vivo and extend those observations to implicate both CD11a and CD11b in that adhesion. In addition, we report that ICAM-1 mediates, in part, the initial leukocyte–endothelial cell adhesion following C5a exposure in vivo.