摘要:

Lucigenin-enhanced chemiluminescence can be measured in 100μl samples of whole, unseparated mouse blood. A procedure for doing so is here described in detail, using a standard clinical luminometer. The assay measures the TPA-induced oxidative burst from granulocytes and macrophages, which is believed to depend on the overall level of inflammation in the body. It is here applied to mice suffering from type II collagen-induced arthritis, and its relation to overt disease symptoms (the arthritis score) is characterised during the course of the disease. A correlation between the assay and the arthritis score is found at the height of the disease (r = 0.42, p =. 039), but not at early or very late time points, although there is a strong hint that the results of an early assay may predict the subsequent disease course. The assay provides a rapid, convenient, quantitative and economical method of assessing disease activity, which can be carried out repeatedly on the same individual. It should be applicable in other mouse models of chronic inflammatory disease. It may find application for rapid screening of novel anti-rheumatic drugs and treatments.

ISSN:0891-6934    

DOI:10.3109/08916939408995690

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Experimental autoimmune thyroiditis (EAT) develops in genetically susceptible mice after immunization with mouse thyroglobulin (MTg), and is mediated by T cells, both CD4+and CD8+, infiltrating the thyroid. Previous work showed that depletion of CD4+, but not CD8+, cells with rat monoclonal antibodies (mAbs) interfered with EAT induction. To test if concomitant CD4+cell depletion and immunization led to EAT resistance, mice were reimmunized at an interval of 15 or 43 days after injection of CD4 mAbs. No resistance had been established; disease severity and anti-MTg titers were comparable to mice with primary immunization. Previous work also showed that treatment during advancing EAT with only CD4 mAbs on days 21, 25 led to long-lasting, reduced severity in EAT, whereas administration of CD8 mAbs alone reduced the smaller CD8+subset only. However, therapy with both mAbs was most efficacious;>50% of thyroids were purged of all cellular infiltrate after only two doses. Moreover, T cells emerging subsequent to depletion were not retained in the thyroid, despite ongoing antibody production. To test if nondepleting CD4 and CD8 mAbs were similarly effective for therapy, mAbs of the IgG2a isotype were administered during advancing EAT. No effect on thyroidal infiltration was observed, indicating that modulation of the CD4 and CD8 antigen without depletion was insufficient for efficacious therapy. To determine if combined therapy with depleting mAbs reestablished self tolerance, treated mice were reimmunized on days 70, 77, when T cell recovery was nearly complete. Thyroiditis was comparable to controls given primary immunization, despite high antibody levels. Thus, efficient depletion of both T cell subsets eliminated immunologic memory of thyroiditogenicity and represents a suitable treatment modality for autoimmune disease.

ISSN:0891-6934    

DOI:10.3109/08916939408995691

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Fifty-five Danish families with two offspring concordant for type 1 diabetes-identified through a nationwide population-based survey, and 57“true sporadic”cases-matched with familial cases for age at onset, but with no IDDM-affected first-degree relatives and long disease duration, and 110 control subjects were typed for putative genetic susceptibility markers for type 1 diabetes identified from a pathogenetic model. The markers included MHC class I, II and III loci, the manganese superoxide dismutase (MnSOD) locus (chr. 6q), interleukin-1β(IL1B), the IL-1 receptor antagonist (IL1RN), and the IL-1 type 1 receptor (IL1RI) loci (each chr. 2q). No significant differences between familial and sporadic cases were found within the MHC region (including the following loci: HLA-DQ,-DR, heat shock protein (HSP) 70, tumour necrosis factor (TNF), HLA-B and-A). In both groups of patients 11% were negative for both DQA1*0301-DQB 1*0302 and DQA1*0501-DQB1*0201 genotypes, and 7% of the type 1 diabetics had genotypes unable to encode a susceptibility DQαβheterodimer. Disease association was found for the IL1RN (p= 0.04) and for the IL1RI (p= 0.03). When comparing controls and only familial cases with type 1 diabetes for the IL1RN polymorphism a difference was observed (p= 0.003). For the IL1B RFLP a trend for difference was observed between familial cases and control subjects (p= 0.046), whereas no differences between sporadic cases and control subjects could be demonstrated neither at the IL1B nor at the IL1RN loci. A difference in the MnSOD pattern was observed between sporadic cases and controls (p= 0.04).

ISSN:0891-6934    

DOI:10.3109/08916939408995692

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Six different hybridomas secreting anti-SCM mAb and one control mAb were placed into adult mice along with [14C] amino acids for biosynthetically labeling. After sacrifice, the14C mAb ascites along with serum, heart, kidney, lung and skeletal muscle were recovered. Tissue associated specific radio-activity (SpAc) and microscopic structural analyses were performed. Confirmation of mAb specificity was by both immunodot blots as well as Western blot analysis. Peritoneal injection of measured doses of anti-SCM mAb yielded tissue SpAc confirming theirin vitrospecificities10. Two of the mAb showed strong reactivity to both renal (GBM) and lung basement membrane (LBM), two were mainly GBM reactive and two showed polyreactivity with a marked reactivity to a Z-line antigen. Autoradiographic light microscopy confirmed that the anti-SCM mAbs bound to both GBM and LBM and to Z-line antigen. Titrated doses of the mAb yielded autoradiographic confirmation in which the grain number on the GBM and LBM increased with increasing dose of mAb for all mAb except the control. This effect was not seen in the muscle tissues but anatomical localization at the Z-line was consistent. The major significance of these studies is the demonstration that circulating antibodies to SCM can reactin vivowith normal mammalian antigens adding confirmation to thein vitrospecificity of these cross-reactive anti-SCM mAbs.

ISSN:0891-6934    

DOI:10.3109/08916939408995693

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

It has been recently reported that human pancreatic islets in tissue culture produce nitric oxide (NO) and show a decreased function when exposed for 6 days to combinations of cytokines (interleukin-1β(IL-lβ) + tumor necrosis factor-α(TNF-α) + interferon-γ(IFN-γ). Here we study the effects of nicotinamide (Nic; 10 or 20 mmol/1) on these deleterious effects of cytokines (50 U/ml IL-lβ+ 1000 U/ml TNF-α+ 1000 U/ml IFN-γ). Islets were isolated from 8 human pancreata at the Central Unit of theβ-Cell Transplant, Brussels, sent to Uppsala and, after 3-5 days in culture, exposed for 6 additional days to the cytokines and/or Nic. The cytokines induced a 6-fold increase in islet NO production (P<0.001), and this effect was partially counteracted by Nic (50-60% decrease in NO production; P<0.001). The cytokines severely decreased the islet insulin content and glucose-induced insulin release (16.7 mmol/1 glucose; 90% decrease; P<0.001). Both these effects of cytokines were partially counteracted by Nic, especially at the highest concentration (20 mmol/1; 2-4-fold increase compared to islets exposed to cytokines alone; P<0.01). Nic by itself did not affect the insulin content or insulin release by control islets. In conclusion, the present data indicate that Nic counteracts the deleterious effects of cytokines on human pancreatic islets. This effect of Nic may be relevant for the beneficial effects of the drug in early IDDM.

ISSN:0891-6934    

DOI:10.3109/08916939408995694

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Rheumatoid factor (RF) is a polyclonal autoantibody directed against the Fc portion of IgG. Although the role of RF in patients with rheumatoid arthritis (RA) is unclear, immune complexes that form between RF and IgG can activate the classical complement (C) pathway, leading to pathogenic outcomes involving inflammatory events and tissue damage. The specificity of serum RF and RF produced by rheumatoid synovial cells (RSC) is different. Serum RF has specificity for rabbit IgG and human IgG subclasses IgGl, 2, and 4, but binds poorly to IgG3. The affinity of serum RF for IgG Fc is low, having an association constant of 104-105M−1. RSC RF, however, has specificity for human IgG and high avidity for IgG3. Because of this greater specificity and avidity for IgG3, and because RSC RF may be pathogenically more important than serum RF, an important role for IgG3-reactive RF in RA may exist. Binding of RF to IgG may be dependent on the allotype and glycosylation of IgG. Infectious agents present in RA patients may directly or indirectly induce the production of certain RF. In this communication, we review and expand on several observations examining the role of IgG3-reactive RF in RA including: 1) binding differences between RF derived from RSC and serum; 2) glycosylation characteristics of IgG and its interaction with RF; 3) apparent allotype dependent binding of IgG3-reactive RF; and 4) possible relationship between infectious agents and the production of IgG3-reactive RF. Taken together, these observations suggest an important role for IgG3-reactive RF in better understanding the etiology and pathogenesis of RA.

ISSN:0891-6934    

DOI:10.3109/08916939408995695

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

The heat shock proteins are a group of evolutionarily conserved proteins with important physiological functions, whose synthesis is enhanced by elevated temperature or other stresses. A role for one or more of these proteins in human autoimmune disease has been extensively discussed. This review considers the evidence of a role for hsp90 in systemic lupus erythematosus (SLE) where over-expression of this protein, its surface localization and auto-antibodies to it have been observed in both human patients and in the MRL/1pr mouse model of SLE.

ISSN:0891-6934    

DOI:10.3109/08916939408995696

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939408995697

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor