International archives of allergy and applied immunology最新文献

After left nephrectomy, 3 10-week old NZB/W mice received orthotopic grafts of kidneys from parental NZW mice of the same age. At autopsy conducted at the age of 33-38 weeks, glomerulonephritis of similar extent was noted in the recipients' own and in the grafted kidneys. Also, very similar granular deposits of immunoglobulins and complement were demonstrated in these kidneys. It was concluded that the absence of glomerulonephritis in NZW mice cannot be attributed to the refractoriness of their kidney to this disease.

We are interested in the physiologic mechanisms of eosinophil activation because of the presumed participation of activated eosinophils in the inflammatory sequelae of asthma. Suspecting that other formed elements of the blood may contribute to such an activation, we examined the capacity of platelet-derived growth factor (PDGF), a product of activated platelets, to activate eosinophils. We found that highly purified monkey and human eosinophils, but not guinea pig eosinophils, were activated by PDGF (superoxide anion production) in a dose-dependent fashion. Moreover, this activation was further dependent on a prior 'priming' of the cells by a brief exposure to subthreshold concentrations of phorbol ester. The response was specific for the BB homodimer of PDGF suggesting it is receptor-dependent.

A simple quantitative method to measure nasal secretion in guinea pigs is described. Nasal secretion was measured with a piece of cotton thread dyed with fluorescein at one end which was inserted into an anterior naris and kept there for 60 s. The stretch of color of a thread dyed with fluorescein was proportional to fluid volume and to increase in weight of a thread due to absorbed nasal secretion induced by nasal provocation. In addition, the stretch of color due to nasal secretion was associated with the score of rhinorrhea. Thus, it is considered that the amount of nasal secretion can be reflected to the length of the stretch of color. Each secretion on the ipsilateral and the contralateral sides induced by nasal provocation could be separately measured by this method. The amount of nasal secretion induced by allergen in passively sensitized guinea pigs could be reduced by pretreatment with ketotifen or flutropium. These results suggest that our method may serve as a quantitative test for nasal secretion in guinea pigs, which would be useful in the study of hypersecretory response in the allergic model or in evaluating the effect of antiallergic drugs on nasal allergy.

Various cells are associated with inflammatory events characteristic of atopic allergy and asthma. As well as T cells and eosinophils, mast cells, basophils, mononuclear phagocytes and platelets have all to be considered particularly as their mediators have potential for contributing directly to the features of bronchial asthma. Nevertheless, mast cell/T lymphocyte/eosinophil interactions may be of particular significance. For instance, the acute symptoms of allergy and asthma such as sneezing, bronchospasm and hives are believed to be largely the result of mediator release from mast cells whereas chronic symptoms (the result of allergic inflammation) can be explained on the basis of eosinophil-mediated tissue damage. Allergen is recognized directly by T cells. Specialized T cell subsets, possibly the Th2 equivalent, predominate in allergy and elaborate IL-4 (an essential co-factor for IgE production) and IL-5 which brings about terminal differentiation and activation of the eosinophil. Basic proteins derived from the crystalloid granule together with PAF and leukotrienes produce chronic wheeze, bronchial irritability, and might also be involved in permanent nasal blockage in chronic rhinitis. This general hypothesis is continually being tested. It is clearly important to identify precise molecular targets in allergy and asthma in order to construct therapeutic strategies.

The C5b-9 complex has a dual role as a factor involved in the initiation of nephritides and in the progress to chronicity and sclerosis. The unique pathophysiology of the membrane attack complex, distinct from other mediators, is its independence from specific receptors. It inserted in any membrane lipid bilayer tested so far.

Based on observations of fluctuations in progenitors for inflammatory cells during allergic responses, we have proposed that a primary determinant of allergic inflammation involves microenvironmental influences on hemopoietic cell differentiation and phenotype; in addition, as a corollary of this, inflammatory cell burden is proposed as an important indicator of the severity and pattern of the inflammatory process in allergy. The studies outlined here focus on the effects of epithelial-cell- and fibroblast-derived cytokines on granulocytic and monocytic cell differentiation and activation in models involving allergic reactions in the upper and lower airways. Pure cultures of nasal or bronchial epithelial cells or fibroblasts are observed to give rise to cytokines important in inducing the differentiation of basophils, eosinophils, neutrophils and monocyte/macrophages. Gene expression, production and secretion of granulocyte/macrophage-colony-stimulating factor, interleukin-6 (IL-6) and IL-8 can be demonstrated in vitro and in vivo. Up-regulation of gene expression and production of these cytokines, which are important in inducing basophil, eosinophil and neutrophil/macrophage differentiation in several assays, is seen with IL-1 and the neuropeptide substance P; conversely, inhibition of cytokine production by structural cells is observed after pretreatment with corticosteroids in vitro, paralleling in vivo effects. Other modulatory effects also examined include: antiallergic compounds, which may affect posttranscriptional events in cytokine production, and heavy metal ions, which can also induce changes in gene expression. Structural-cell-derived extracellular matrices appear also to be important both in mast cell differentiation and in macrophage cytokine gene expression, both of which potentially feedback upon chronic allergic inflammatory processes, leading to their perpetuation.(ABSTRACT TRUNCATED AT 250 WORDS)

In 23 patients with allergic rhinitis, biopsies of the nasal mucous membrane were taken at one of the following times after challenge of one nostril with allergen: 0 (baseline) (n = 7), 1/2 h (n = 6), 1 h (n = 5), and 2 h (n = 5). In the nostril stimulated by allergen there was a transient early phase influx of eosinophils while the numbers of stainable mast cells decreased, probably due to their degranulation. In the contralateral unstimulated nostril, there was no change in numbers of eosinophils but the numbers of stainable mast cells decreased. These results support the proposed role in allergic rhinitis of the mast cell and eosinophil, and suggest that the eosinophil may be a rapidly mobilized effector cell.

The low-affinity receptor for IgE (Fc epsilon RII, CD23) and the related soluble IgE-binding factors (IgE-BF; sCD23) play an important role in IgE regulation. Sera of patients suffering from atopic dermatitis (AD) were reported to contain an IgE-binding component with a molecular weight of 60 kD. The aim of our studies was the isolation and characterization of the 60 kD component. Sera of patients with AD were fractionated by ammonium sulfate precipitation (10-90%). The fractions were analyzed with regard to their IgE and their IgE-BF contents. Furthermore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and subsequent autoradiography with 125I-labeled human IgE (PS) was performed to detect IgE-binding activity. The major amount of IgE as well as IgE-BF was obtained within the 30-50% ammonium sulfate precipitation. In addition, IgE-binding activity was precipitated at 60% saturation. Separation by gel filtration under physiological conditions indicated IgE-BF with molecular weight of greater than 100, 60, 25 and 15 kD. Rechromatography of the greater than 100-kD fraction led to IgE-binding activity with a molecular weight of 60 kD which is not present within normal sera. The data demonstrate that the 60-kD component is partially bound to serum IgE. One may suggest that the complex is involved in the induction and persistence of allergic disorders.

We have previously reported that topical exposure of mice to oxazolone results in the appearance of regulatory mechanisms which markedly depress lymph node cell (LNC) proliferative responses to subsequent challenge with the same chemical. In the present study, we have sought to identify the cellular targets for such immunoregulation. Autoradiographic analyses revealed that although pre-exposure to oxazolone caused a substantial reduction of paracortical hyperplasia following challenge, the frequency of proliferating cells in lymphoid follicles was slightly increased. That B lymphocyte responses are unaffected by oxazolone-induced immunoregulation was confirmed by investigation of anti-hapten antibody formation by draining LNC. Challenge with oxazolone resulted in an accelerated antibody response in mice previously exposed to the same chemical. These data reveal that the active immunoregulation induced following sensitization with oxazolone is selective for T lymphocytes. Evidence is presented that CD4+ and CD8+ T lymphocytes possess equivalent sensitivity to these mechanisms.