摘要:

The stimulation of human vascular endothelial cells with P. falciparum‐infecterylhrocytes resulted in the non‐transient up‐regulation ofICAMexpression on human endothelial cells. The induction was independent fromTNFas assured in various controls including the application of aTNF‐neutralizing antibody. The possibility that TNF is produced by endothelial cells was investigated in a purified culture of human endothelial cells byTNF‐ELISAandTNF‐bio‐assay both with negative results. This result may be evidence of the existence ofTNF‐independent mechanisms in the pathogenesis of human c

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03365.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The authors demonstrated previously that a short‐term treatment with IL‐6 of lymphokine‐activated killer (LAK) cells produces an increase in cytotoxic activity of CD56+/CD3−effector cells generated from human PBL as well as from human thymocytes. In the study described here, the mechanisms by which IL‐6 enhances LAK cytotoxicity were examined. Like untreated LAK cells, IL‐6‐treated LAK cells require Ca++to initiate cytolysis. However, IL‐6 treatment of LAK cells does not alter the rate of programming for lysis. Instead, IL‐6 increases target‐binding capacity of CD56+/CD3−LAK cells in association with the increased cytotoxicity. Similar to target‐binding of untreated LAK cells, the binding between IL‐6‐treated LAK cells and target cells is dependent on Mg++. Cellular adhesion molecules (CAM), CD1 la‐c, CD18. CD54. CD56, CD58 and CD2 (T11, epitope). are up‐regulated in LAK cells by culture with IL‐2. Among MoAbs to these CAMs. only Abs to CD11a/CD18 (LFA‐1) and CD54 (ICAM‐1) decrease both target‐binding and cytolysis by LAK cells. IL‐6 treatment changes neither the proportion nor the intensity of CAM positive cells. However, MoAbs to CD11a/CD18 and CD54 reduce both target‐conjugation and cytotoxicity of IL‐6‐enhanced LAK cells to the same level as control LAK cells treated with the MoAbs. IL‐6‐enhanced LAK functions (both target‐conjugation and target‐lysis) are not abrogated by MoAbs to other CAM which do not inhibit standard LAK functions. These results indicate that IL‐6 up‐regulates cellular events mediated by CD11a/CD18 and CD54 molecules which are involved in standard LAK functions. These events may result in activation of lytic efieclor cells, associated with an

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03366.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Lipopolysaccharide (LPS) prepared from a rough mutant ofSalmonella typhimuriumand deacylated enzymatically (dLPS) does not promote neutrophil adherence to human umbilical vein endothelial cells (HUVECs). This paper reports that similarly, a smooth form of LPS prepared fromYersinia enlerocoliticaO:3, a serotype known to trigger reactive arthritis in humans, and treated with alkali (yersinia LPS‐OH) failed to augment neutrophil adherence to HUVECs. Studies of the mechanism underlying the poor augmentation revealed that neither enzymatically deacylated LPS fromEscherichia coliJ5 (J5 dLPS) nor yersinia LPS‐OH stimulated expression of endothelial cell adhesion molecules E‐selectin, VCAM‐1 and ICAM‐1, whereas both Intact J5 LPS and yersinia LPS were stimulatory. Impaired up‐regulation could not be explained by decreased binding of yersinia LPS‐OH to HUVECs. Furthermore,51Cr‐labelled HUVECs treated with different concentrations of yersinia LPS‐OH released51Cr in the presence of anti‐yersinia anti‐0 antibody and complement. J5 dLPS and yersinia LPS‐OH inhibited up‐regulation of the adhesion molecules induced by J5 LPS and yersinia LPS but not that induced by tumour necrosis factor alpha.Taken together, the results suggest that although yersinia LPS‐OH can depress development of acute inflammation by inhibiting up‐regulation of etidothelial‐cell adhesion molecules, sufiicient LPS‐OH is bound to induce cell injury and thereby inflammation in the prescence of specific antibody and complement. The findings may have pathogenetic implications in yersinia‐triggered reactive arthritis characterized by dissemination

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03367.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Interaction of ICAM‐1 and its ligands plays an important role in the leukocyte binding to endothelium. The best characterized ICAM‐ligands belong to the family of ß2‐integrins (CD11/CD18), but recently it has been suggested that CD43, a molecule with no structural resemblance to integrins binds ICAM‐1 also. On the leukocytes the main regulatory pathway for ICAM‐mediated binding is believed to be a short‐term regulation of the avidity of CD11/CD18. In this study the authors investigated whether a quantitative increase in the surface expression of ICAM‐ligands also can lead to enhanced binding to purified ICAM‐I. PM A‐treatment differentiates myelomonocytic cell lines into macrophages with a concomitant increase in the surface expression and mRNA‐levels of the ß2‐integrin α‐ and ß‐chains as well as that of CD43, another ICAM‐ligand. The binding of the PMA‐treated THP‐1 ceils to ICAM‐1 was increased simultaneously compared to non‐treated cells. The binding was blocked completely with antibodies to CD18 and ICAM‐I. It is concluded that in addition to the transient qualitative regulation, a long‐term quantitative regulation of ICAM‐1 ligands also plays a role in increasing the adhesiveness of myelomonocytic cells. This may

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03368.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

CZ‐1 is a novel sialic acid‐dependent epitope of the murine CD45RB molecule which is expressed on cells that proliferate when cultured in IL‐2. Because IL‐2 appears to be Important in the differentiation of NK cells, the authors examined the expression of CZ‐1 on immature NK‐Iineage cells within the bone marrow. All mature NK1.1+cells as well as their NK1. l−IL‐2 responsive precursors were CZ‐1+. Furthermore, IL‐2 unresponsive transplantable NK progenitor cells expressed CZ‐1 also. To examine expression of CZ‐1 on other immature lymphoid progenitor cells. CZ‐1+and CZ‐1 marrow cells were tratisplanted Into lightly irradiated scid mice. Transfer of CZ‐1+cells resulted iti rapid and sustained generation of thymocytes and splenic B cells, whereas CZ‐1−cells caused delayed repopulation. This suggested that the slowly repoptilating pluripotent stem cells lacked CZ‐1. Therefore, expression of CZ‐1 on Ly66Lin−c‐kit+cells, highly enriched for pluripotent stem cells, was examined. This population appeared lo be homogeneously CZ‐1dull. Thus, it appears that expression of CZ‐1 is developmentally regulated, with diflerentiation associated with increased expression. Since CZ‐1 is expressed on a protein tyrosine phosphatase, it is likely that this molecule regulates

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03369.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Cellular responses to several purified antigens oi Mycobacterium bovis were examined in experimentally infected cattle over a period of 36 months, using in vitro cellular proliferation and interferon‐γ assays. These antigens (12, 19, 22a, b. 24, 25.30, 32, 39.65 and 70 kDa) included the majority of M. /lom protein antigens described to date and are highly homologous to those purified fromM. tuberculosis. Cellular responses vi'ere examined at 3‐month time intervals during the 36‐month course of infection. All purified antigens induced cellular immune responses in the infected animals. The onset and magnitude of response to individual antigens varied among the animals. At any specific time during the period of infection one or more antigens appeared to be immunodominant but the immunodominance profile changed as the infection progressed. Humoral immune responses were low or absent in the first half of the infection period, but increased substantially for some of the antigens during the second half. Variation was observed among the different animals as to which antigens they reco

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03370.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Polyclonal human secretory IgAI and lgA2 antibodies to a bacterial protein antigen Streptococcus mutans Agl/II, and polyclonal human serum IgA1 and IgA2 antibodies to staphylococcal a‐toxin, were found to interfere with antigen‐mediated C3b fixation. In fluid phase, immune complexes of antigen and IgA failed to fix C3b, whereas antigen‐IgG complexes did fix C3b. Partial removal of glycan chains with Streptococcus mitis SK96 glycosidases diminished the capacity of IgA antibodies to interfere with antigen‐mediated C3b fixation by the alternative complement pathway. The authors conclude that native serum or secretory IgA antibodies suppress C3b fixation, and that the glycan chains play a significant role in maintaining this p

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03371.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Vitronectin occupies the metastable binding site of C5b‐7, which is unable to insert membranes as part of the complement lytic attack. Some evidence has been presented that vitronectin inhibits also membrane‐associated pore formation by inhibiting C9 polymerization in the terminal complement complex (TCC). The authors wished to add to this background by studying the effect of vitronectin on formation of TCC on a carbohydrate surface like agarose beads, an alternative complement pathway activator. Bound TCC was detected by monoclonal and polyclonal antibodies to C9‐neoepitopes. Soluble SC5b‐7 and TCC (SC5b‐9) did not bind to the agarose beads. Using serum or isolated complement factors for the alternative and terminal pathways, the authors found that vitronectin reduced the density of C9‐neoepitopes on the beads. As there was no convincing evidence for association of vitronectin with the factors C5b‐8 of the agarose‐bound TCC, it was concluded that vitronectin bound directly to C9 in TCC and inhibited C9 polymerization within the complex. The authors have shown that TCC can bind to a carbohydrate surface like agarose (an alternating polymer of galactose moieties) in the absence of lipid. These results suggest that vitronectin can limit the lytic effect of membrane‐bound TCC by inhibiting

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03372.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

To investigate the mechanisms of action underlying the therapeutic effect of CD4 monoclonal antibody therapy in rheumatoid arthritis (RA), clinical responses were compared with several laboratory parameters. Twenty‐nine RA patients received either 10 mg, 50 mg or 100 mg of cM‐T412, a chimeric CD4 MoAb, for 7 days. The CD4 binding sites on circulating lymphocytes were saturated directly with cM‐T412 and serum levels of unbound cM‐T412 accumulated towards day 7 of treatment only in the patients treated with 50 and 100 mg. The treatment induced an instant and prolonged depression of the number of circulating CD4+cells, similar for all dosages. Clinical improvement was observed predominantly in the patients treated with 50 or 100mgcM‐T412daily and did not correlate with changes in counts of circulating leucocyte subsets nor with changes in serum cytokine levels. An antiglobulin response against cM‐T412 developed in a majority of the patients. Side effects on the first day of treatment were correlated with an increase of serum IL‐6 levels. This study indicates that a favourable clinical effect of cM‐T412 administration was associated with the presence of unbound cM‐T412 in the circulation of RA patients. Therefore penetration of unbound cM‐T412 into the site of inflammation might determine the thera

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03373.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Variable immunoglobulin heavy‐chain regions (VDJ) of two newly established human lymphoma cell lines (HF‐1 and HF‐4) were sequenced. The most homologous germline VHgene found for both the HF‐1 and HF‐4 sequences was VH26 of the VH3a (V gene) family (82% and 91 % homologies, respectively). The JHregion of the HF‐4 heavy‐chain sequence contained two nucleotide differences compared to the published germline JH3 gene. The DHJHregion of the HF‐1 gene had a record high number (20%) of somatic mutations.The numerous hypermutations found in the HF‐1 cell line support the hypothesis that in some human follicular lymphomas, mutations continue to accumulate in immunoglobulin genes during the malignant growth. Follicular lymphoma cell lines, which have an active mutational machinery, in future may help to solve the molecular events behind the somatic hypermutations modifying immunoglobulin genes

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03374.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY