摘要:

TNF plays a central role in septic shock induced by endotoxin or Gram‐negative bacteria. Zymosan can elicit a septic shock‐like syndrome in rodents in the absence of endotoxin. TNF and IL‐6 release in mice treated with zymosan was investigated. One hour after intraperitoneal zymosan injection, maximal TNF levels were measured in serum, followed by IL‐6 peak levels 1 h later. Treatment with a monoclonal antibody against TNF lowered zymosan‐induced mortality from 63 to 11.6%, while maximal IL‐6 levels were lowered by about 40%.Mechanisms triggering zymosan‐induced cytokine release in murine macrophages were analysed in vitro. Cytokine release was only slightly triggered by uncoated zymosan particles. Thirty‐nine per cent of TNF release by macrophages appeared to be triggered by zymosan‐bound activated complement. Maximal TNT release also required the presence of natural antibodies against zymosan and zymosan‐activated scrum. In contrast, maximal 11–6 release was reached upon stimulation with zymosan‐activated serum only, while the presence of zymosan particles lowered this response.We conclude that TNF is a crucial mediator m zymosan‐induced shock. TNF release can be induced by different immunological pathways, without the need for the direct presence of endotoxins. Although IL‐6 release during septic shock is partly dependent on TNF. in vitro trigger mechanisms for IL

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02925.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Beta‐1, 3‐D‐polyglueose derivatives protect mice against otherwise lethal bacterial infections This protective effect has previously been considered to be mediated through mononuclear phagocytes. We have now investigated the cellular composition in blood and peritoneal fluid after administration of the β‐1,3‐D‐polyglucose before and after challenge withEscherichia coli.In animals treated with β‐1,3‐D‐polyglucose derivatives, the total white cell number was significantly increased in both blood and peritoneal fluid before and after challenge withE. coli.The increased total cell number was mainly the result of raised levels of granulocytes. The effects of β‐1,3‐D‐polyglucose‐derivatized microbeads (GDM) and soluble aminated β‐1,3‐D‐polyglucose (AG) were similar.Bacterial counts in peripheral blood in GDM‐ and AG‐treated animals increased until 6 h after challenge and approached zero after 24 h. In untreated animals the bacterial counts increased gradually until the animals died after about 12 h. Bacterial counts in peritoneal fluid of GDM‐and AG‐treated animals declined to zero after 24 h. In untreated animals there was a slight increase in bacterial counts until the animals died after about 12 h.By using radioactive labelling, we localized the bacteria as well as the β‐1,3‐D‐polyglueosc derivatives during the period following injection. Particle‐bound β‐1,3‐D‐polyglucose was recovered mainly in the milky spots of the omentum. A conspicuous number of bacteria were also recovered in the milky spots. The soluble aminated β‐1,3‐D‐polyglucose was recovered mainly in the liver. However, on a weight basis,

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02926.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The influences of pretreatmeni with β‐1.3‐D‐polyglucose derivatives on levels of cytokines and arachidonic acid metabolites in body fluids in experimental peritonitis in mice are reported. Peritonitis was induced by an intraperitoneal injection of 108liveEscherichia coli.Pretreated animals survived the infection, untreated animals died about 12 h after inoculation withE. coli.Levels of IL‐l in plasma and peritoneal fluid, measured by cytotoxicity assay of the HT‐2 cell line, increased significantly during the first 48 h after intraperitoneal treatment with β‐1.3‐D‐polyglucose‐derivalized microbeads (GDM) or soluble, animated /β‐1,3‐D‐polyglucose (AG). After subsequent challenge withE. coli.the levels of IL‐1 were significantly lower than in untreated animals. There was no increase in levels of TNF after treatment with GDM or AG, measured by cytotoxicity assay of the WEHI clone 13 cell line. After challenge withE. coli.TNF in plasma and peritoneal fluid was significantly lower compared with untreated animals. Both PGE2; and LTB4. measured by radioimmunoassay kits, were increased in peritoneal fluid alter treatment with GDM and AG. After challenge withE coli.PGE2and LTB4in peritoneal fluid increased to about half the concentration of infected control animals. Intraperitoneal injection of indomethacin to pretreated animals resulted in increased levels of IL‐l and TNF‐ and decreased levels of PGE2; following challenge withE. coli.The levels of IL‐1 and TNF remained elevated until the animals died after about 12 h.These studies demonstrate that the raised levels of arachidonic acid metabolites after pretreatment with GDM or AG seem to inhibit the otherwise lethal elevation of IL‐1 and TNF in body fluid

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02927.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Amyloid fibril material was extracted from autopsy material of a patient who died from progressive cardiac failure at age 64. He had an enlarged heart on routine X‐ray at age 47 and the first symptoms of cardiac failure at age 62. Fractionation of the fibril material resolved peptide fragments immunoreactive with anti‐human transthyretin (TTR). One of the peptides was farther purified by high‐performance liquid chromatography (HPLC) and subjected to tryptic peptide mapping along with TTR isolated from the patient's serum. In both instances, sequencing procedures revealed, in addition to the normal peptide 12 (residues 105 126). an abnormal peptide with an isoleucine for valine substitution at position 122. This substitution has been described previously in a patient with systemic senile amyloidosis (SSA) homozygous for this variant. The results question whether SSA is a clinical entity related to TTR He 122 with phenotypic expression in the homozygous cond

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02928.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The CD5 membrane molecule, initially identified as an exclusive T‐cell marker, also defines a phenotypically and functionally distinct B‐lymphocyte population. In normal individuals, CD5+B cells are committed to secrete‘natural’polyreactive (auto)antibodies, that is antibodies, mainly IgM, endowed with multiple antigen‐binding capabilities, including rheumatoid factor (RF) activity. At variance with this, in rheumatoid arthritis (RA) as well as in other autoimmune conditions, monoreactive autoantibodies binding with high affinity and specificity to a given self antigen have been isolated and the cells from which they originate differently related to the CD5+B‐lymphocyte subset.Here, we studied the proportions of CD5+B cells and the characteristics, in terms of polyreactivity and monoreactivity, of RF produced by B lymphocytes in RA patients with classified disease activity. Our results suggest that patients with a more severe disease activity have higher proportions of CD5+B cells and higher frequencies of B lymphocytes committed to secrete RF, with the characteristics of polyreactive antibodies. On the other hand, we did not find a significant difference between the proportions of peripheral B cells producing monoreactive RF in patients with high‐ versus patients with low‐activity RA. However, in two highly active RA patients, we found that synovial fluid, compared with peripheral blood, was significantly enriched for (IgG and IgA) monoreactive RF‐

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02929.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Accessory cells (AC) are believed to play two major roles in T‐cell activation: they cross‐link certain stimuli such as monoclonal antibodies, and they provide needed cytokines. To differentiate between these roles, we cross‐linked OKT3 on highly purified T‐cells by means of Fc‐specific goat anti‐mouse IgG‐coated polystyrene heads and studied T‐cell activation after exogenously added cytokines. Following addition of AC, rIL‐2. or rIL‐1. CD25 was up‐regulated, and the cells proliferated and became cytotoxic. Both CD4+and CD8+cells were activated in the presence of AC or rIL‐2. In contrast, only CD4+CD29+CD4SRA cells responded in the presence of rIL‐1. Anti‐IL‐2R p55 (anti‐TAC) monoclonal antibody inhibited the proliferative response supported by rIL‐2 or rIL‐1. To inhibit proliferation of cells stimulated in the presence of AC. anti‐TAC needed to be supplemented with anti‐IL‐6 antibodies, or to be added in a 10‐fold higher concentration. Cultures with AC produced larger amounts of IL‐2 than those supplemented with rIL‐1. Only AC‐containing cultures also produced detectable amounts of IL‐6. These findings combined with the observation that none of 2000 purified T cells counted in each of six independent experiments expressed MHC class II antigens strongly suggest that rIL‐I can activate T cells directly, rather than indire

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02930.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Thymocytes were removed from mice at different times before and after birth, and their phenotype and killing repertoire were analysed after stimulation with human recombinant interleukin 2 (IL‐2). Whereas three different tumour targets were killed by all lymphokine‐activated killer (LAK) populations tested. EL4 lymphoma cells were only killed by LAK cells derived from thymocytes after, but not before, birth. Cold‐target competition tests showed that LAK thymocytes recognized antigenic structures on EL4 cells that arc different from those on other tumour targets. Analysis of EL4 target killing after removal of different subsets from LAK cells revealed that the major part of this killing is exerted by CD8+cells. Our findings are additional and more direct evidence for partial target specificity in LAK

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02931.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02932.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY