摘要:

AbstractOver the past 12 years, the poxvirus vector technology has provided scientists with valuable reagents to achieve high‐level expression of proteins, to address questions of structure‐function relationship of specific polypeptides, to investigate the immunobiology of specific pathogens, and to develop recombinant vaccine candidates. It is this last role that has drawn enthusiasm from the medical community because of the potential this technology has to provide novel approaches for addressing urgent needs in human and veterinary medicine. From one perspective, the safety issues surrounding the use of vaccinia‐based vaccine candidates have been addressed with the development of the NYVAC and ALVAC vectors. Evaluation of these novel poxvirus vectors are in progress to determine their potential impact on cancer and infectious disease.J. Leukoc. Biol.58: 1–13; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.1

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractStem cell factor (SCF) is the ligand for the tyrosine kinase receptorokit, which is expressed on both primitive and mature hematopoietic progenitor cells. In vitro, SCF synergizes with other growth factors, such as granulocyte colony‐stimulating factor (G–CSF), granulocyte macrophage–colony‐stimulating factor, and interleukin‐3 to stimulate the proliferation and differentiation of cells of the lymphoid, myeloid, erythroid, and megakaryocytic lineages. In vivo, SCF also synergizes with other growth factors and has been shown to enhance the mobilization of peripheral blood progenitor cells in combination with G–CSF. In phase I/II clinical studies administration of the combination of SCF and G‐CSF resulted in a two‐ to threefold increase in cells that express the CD34 antigen compared with G–CSF alone. Other potential clinical uses include ex vivo expansion protocols and in vitro culture for gene therapy.J. Leukoc. Biol.58: 14–22; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.14

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractExamination of the proliferative responses in vitro to mitogens (concanavalin A, phytohemagglutinin, lipopolysaccharide) of spleen cells recovered from C57B1/6 mice during blood‐stagePlasmodium chabaudiAS infection revealed that the most severe suppression occurred during the first 14 days post infection, that is, during the acute phase of infection. Coincidently, inducible nitric oxide synthase gene expression was found to be up‐regulated in the spleens of infected mice, and both splenic and peritoneal macrophages produced high levels of NO in vitro in response to stimulation with lipopolysaccharide (LPS). The roles of NO, a molecule recently found to mediate immunosuppression during parasitic infections, and of the well‐recognized immunosuppressive molecule prostaglandin were, therefore, investigated in the suppression of proliferation to mitogens and specific antigen of spleen cells from 7‐ and 14‐day P.chabaudiAS–infected mice. Addition of either 0.5 mMNG‐monomethyl‐l‐arginine (L‐NMMA) or 0.5 mM aminoguanidine (AG), inhibitors of NO synthase, or 10 μg/ml indomethacin (INDO), a prostaglandin inhibitor, partially but significantly abrogated the suppression in response to concanavalin A (Con A) and phytohemagglutinin (PHA). Only the addition of INDO significantly increased the responses to LPS. Addition of L‐NMMA or AG in combination with INDO partially but significantly abrogated the suppression in response to Con A and completely abrogated the suppression in response to PHA. The addition of L‐NMMA or AG also significantly increased proliferation in response to parasite antigen. The contribution of NO to suppression of lymphoproliferation was confirmed by adding 3‐morpholino‐sydnonimine‐hydrochloride (SIN‐1), a chemical generator of NO, to mitogen‐stimulated splenocyte cultures prepared from normal mice. The mechanism of NO‐mediated suppression was investigated in coculture experiments using spleen cells from normal mice and peritoneal macrophages from either normal or day 7 infected mice. The addition of 5‐10 104peritoneal macrophages from infected mice significantly and consistently suppressed Con A– or PHA‐stimulated proliferation of normal splenocytes. Moreover, suppression correlated with production of NO and could be reversed by the addition of L‐NMMA or AG. These results suggest that, in addition to prostaglandin, increased NO production by macrophages within the first 2 weeks after infection withP. chabaudiAS contributes to immunosuppression associated with blood‐stage malaria.J. Leukoc. Biol.58: 23–31; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.23

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractOils 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 aSalmonella typhimuriumchallenge. 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 108colony‐forming units ofS. 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 anS. typhimuriuminfection occurs early, the reduced function of the Kupffer cells is probably a major factor.J. Leukoc. Biol.58: 32–39; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.32

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have examined the role of CD66 in the modulation of neutrophil adhesion and effector function. Engagement of neutrophil CD66 with anti‐carcinoembryonic antigen (anti‐CEA) Ig results in activation‐associated phenomena including shape change, activation of β2‐integrins, and priming of the respiratory burst. Anti‐CEA Ig‐treated neutrophils underwent transient shape change distinct from that induced by formyl‐Met‐Leu‐Phe (fMLP). fMLP stimulated β2‐integrin up‐regulation and 70% loss of L‐selectin, whereas only low‐level up‐regulation of the β2‐integrins, without loss of L‐selectin, occurred with anti‐CEA Ig. Anti‐CEA F(ab')2fragments and whole Ig augmented β2‐integrin‐dependent adhesion. Anti‐CEA Ig‐induced β2‐integrin activation was transient, whereas fMLP‐induced activation persisted longer. Although they did not cause a significant increase in respiratory burst activity, CEA Ig and F(ab')2fragments of antibody primed neutrophils so that the subsequent fMLP‐induced respiratory burst was significantly increased.J. Leukoc. Biol.58: 40–48; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.40

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWe evaluated two independent models of eosinophil differentiation for their ability to synthesize the ribonuclease toxins eosinophil‐derived neurotoxin (EDN) and eosinophil cationic protein (ECP). Cells from the done 15 subline of HL‐60 (human promyelocytic leukemia) produced both EDN and ECP; production of EDN increased in response to butyric acid (BA). CD34+peripheral blood progenitor cells (PBPCs) grown with cytokines promoting eosinophil differentiation also produced EDN. EDN from both the done 15 and PBPCs was more heterogeneous and heavily glycosylated (~22–45 kDa) than EDN from mature peripheral blood eosinophils (18–25 kDa). The heterogeneity of EDN from the done 15 cells was not altered by endogiycosidase Hf, whereas treatment with peptide‐N‐giycosidase F (PNGase F) produced a single‐band immunoreactive band (~15 kDa). In contrast, only the highest molecular weight forms of EDN from differentiated PBPCs were eliminated by PNGase F (reduced to 22–35 kDa), suggesting the presence of uncharacteristic forms of posttranslational modification. Synthesis of hyperglycosylated proteins has not been previously reported in PBPCs and is a feature shared with tumor cells and cell lines.J. Leukoc. Biol.58: 49–54; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.49

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractGc globulin (vitamin D binding protein) has been shown to augment significantly die leukocyte chemotactic activity of the activated complement peptides C5a and C5a des Arg. However, the mechanism of chemotaxis enhancement is not known. Natural C5‐derived peptides contain a carbohydrate side chain that comprises approximately 25% of the mass of the 11‐kDa peptides. Previous studies have demonstrated that Gc globulin binds to C5‐derived peptides via sialic acid residues on this carbohydrate side chain. The necessity of this carbohydrate side chain for chemotaxis enhancement by Gc globulin was investigated by using both natural (glycosylated) and recombinant (carbohydrate‐free) peptides. The dose‐response curves of neutrophil chemotaxis to recombinant C5a or C5a des Arg plus Gc globulin were identical to those observed with the naturally derived peptides, despite the fact that natural C5a bound to Gc globulin while the recombinant C5a failed to bind this protein. Moreover, neutrophils pretreated with Gc globulin then washed before addition to the chemotaxis assay displayed significantly enhanced movement to C5a alone. These results indicate that the binding of C5a/C5a des Arg to Gc globulin is not necessary for their chemotactic activity to be augmented. Furthermore, these results demonstrate that the co‐chemotactic activity of Gc globulin is generated on the cell surface, independent of C5a binding to its receptor.J. Leuhoc. Biol.58: 55–58; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.55

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractExposure to hypochlorous acid (HOC1), the main product of the reaction of neutrophil myeloperoxidase (MPO), H2O2, and Cl‐, reportedly decreases apotransferrin's iron binding capacity. Optimal transferrin iron binding requires the coexistent binding of anions such as bicarbonate (HCO3‐) near the protein's two iron binding sites. Recently, we found that if HCO3‐was also present during HOC1 exposure, apotransferrin retained its ability to inhibit iron‐catalyzed hydroxyl radical generation. Therefore, we examined apotransferrin iron binding capacity after exposure to the MPO/H2O2/I‐system in the presence and absence of several anions (HCO3‐, H2PO4‐, SO42‐, and ClO4‐) known to bind to apotransferrin. Although the MPO system decreased apotransferrin iron uptake to only 46% of the untreated apotransferrin control, apotransferrin treated in the presence of 1 mM HCO3‐or H2PO4‐retained 84 and 74%, respectively, of its iron binding capacity. Similar results were seen when apotransferrin was treated with NaOCl. These results could not be explained on the basis of a loss of MPO activity or scavenging of HOCl. In contrast, SO42‐and ClO4‐were unable to prevent the MPO‐mediated loss of apotransferrin iron binding capacity. NaOCl had no effect on the ability of transferrin to bind any of these anions, as assessed by the anion‐induced change in apotransferrin absorbance spectrum. HCO3‐but not H2PO4‐, SO42‐, or ClO4‐decreased MPO‐mediated oxidation (iodination) of apotransferrin. Under some conditions H2PO4‐actually increased apotransferrin iodination. HCO3‐and H2PO4‐may protect apotransferrin from MPO‐mediated oxidative damage by preventing selective oxidation of one or both iron binding sites. This process may allow transferrin to retain its iron binding function during MPO exposure in vivo.J. Leukoc. Biol.58: 59–64; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.59

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractReactive oxygen intermediates (e.g., superoxide [O2‐]) generated by microglia may play a role in host defense and injury within the central nervous system. We investigated the effect of cytokines on human microglial cell O2‐production on stimulation with phorbol myristate acetate. Priming of microglial cell cultures with interferon‐γ or tumor necrosis factor‐α resulted in a dose‐ and time‐dependent enhancement of (O2‐production. The priming effects of these cytokines were mediated through a protein kinase C signal transduction pathway. In contrast, astrocytes did not generate detectable O2‐on phorbol myristate acetate stimulation. Treatment of microglia with transforming growth factor‐β, interleukin‐4, or interleukin‐10 suppressed in a dose‐dependent manner the priming effects of tumor necrosis factor‐α and interferon‐γ. The results of this study have implications for understanding the mechanisms by which cytokines and microglia contribute to processes of host defense and neurodegeneiration via generation of reactive oxygen intermediates.J. Leukoc. Biol.58: 65–70; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.65

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWe investigated the effect of interleukin‐1 (IL‐1) activation of human umbilical vein endothelium (HUVE) on human monocyte transendothelial migration induced by chemotactic factors. Monocyte migration across unacdvated endothelium in response to macrophage inflammatory protein‐lα (MIP‐1α), RANTES, platelet‐activating factor (PAF), or monocyte chemoat‐tractant protein‐1 (MCP‐1) was completely inhibited (90%) by monoclonal antibodies (mAbs; 60.3) to CD 18 of the CD11/CD18 complex on the monocyte and partially inhibited (by 75%) in response to C5a. When the HUVE was stimulated with IL‐lα (5 h, 0.1 ng/ml), monocyte migration in response to C5a, MIP‐lα, RANTES, or PAF was no longer inhibited by mAb to CD18. However, migration was blocked by the combination of mAb to the (α4‐integrin (CD49d) chain of very late antigen‐4 (CD49d(/CD29) with the mAb to CD18. In contrast to the above stimuli, activation of the HUVE with IL‐1α inhibited the transendothelial migration of monocytes in response to MCP‐1. mAbs to the adhesion molecules up‐regulated on HUVE by IL‐1, i.e., E‐selectin (CD62E), intercellular adhesion molecule‐1 (CD54) or vascular cell adhesion molecule‐1 (CD106), did not reverse the inhibitory effect. Transendothelial migration in response to MCP‐1 but not to C5a was inhibited by the treatment of monocytes with culture supernatant from IL‐1α‐stimulated (but not from unstimulated) HUVE. Such supernatant contained chemotactic activity for monocytes, and a mAb to MCP‐1 blocked the migration inhibitory effect of IL‐1 activation of the HUVE monolayer, as well as the chemotactic activity in the supernatant from IL‐1‐stimulated HUVE. The inhibitory effect on migration of IL‐1‐stimulated HUVE was specific for monocytes because polymorphonuclear leukocyte transendothelial migration in response to IL‐8 (a related chemokine) was not inhibited by IL‐1 activation of HUVE. These results demonstrate that: (1) C5a but not MCP‐1, MIP‐lα, RANTES, or PAF activates not only a CD 18‐dependent but also a VLA‐4‐dependent mechanism on monocytes, which mediates migration across unstimulated HUVE; (2) IL‐1 (tumor necrosis factor‐α or lipopolysaccharide) activation of HUVE results in efficient VLA‐4 (CD494/CD29)‐mediated monocyte transendothelial migration in response to C5a, RANTES, MIP‐1α, and PAF, in addition to the CD 18‐dependent pathway, but inhibits the response to MCP‐1; and (3) this selective inhibition is probably due to MCP‐1 production by the activated endothelium monolayer and may be one mechanism of down‐regulation by the endothelium of monocyte migration in response to extravascular MCP‐1.J. Leukoc. Biol.58: 71–79,1995.

ISSN:0741-5400    

DOI:10.1002/jlb.58.1.71

出版商:Wiley    

年代:1995

数据来源: WILEY