摘要:

AbstractThe atopic phenotype develops on the basis of a genetic predisposition. Several candidate genes and chromosomal regions have been recently identified that may play a role in the development of allergic sensilization and total IgE production, including genes encoding MHC and T‐cell receptor (TCR) molecules, cytokines and others. Genetic predisposition triggers and immunological dysregulation which is controlled by CD4+T‐cells. (Specialized) antigen presenting cells process and present allergenic peptides (T‐cell epitopes) on MHC class II molecules to T‐cells that recognize MHC plus peptide using the TCR. Cognate and non‐cognate interaction results in T‐cell activation. Selective stimulation of the allergen specific T‐cells is the result of allergen‐specific sensitization. These T‐cells are characterized by (simultaneous) production of IL‐3, IL‐4, IL‐5 (and may be IL‐13). These cytokines control the production of IgE by B cells and play a critical role in the activation and differentiation of effector cells of the allergic response (such as eosinophils and mast cells). In additon to MHC‐TCR interaction and cytokine production, ligation of CD40 and CD40L represents an additional requirement for the production of functional IgE molecules. Immediate hypersensitivity responses are characterized by an early phase response (triggered by many mediators released from effector cells following allergen exposure. IgE cross‐linking and activation of signal transduction pathways) and a late phase response that is mediated to a large extend by the influx of T‐cells and effector cells into the site of allergic inflammation. Deliniation of the immunological mechanisms that result in allergic sensitization will contribute to the development of specific immunomodulatory strategies aimed to preve

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00242.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThis investigation was conducted when previously rcpealable experimental data became impossible to reproduce when using keratino‐cytes cultured in serum‐free medium. Differences in calcium molarity between batches of medium were identified as a source of variation in cultured keratinocyte populations. The susceptibility of cultured keralinocytes to even small alterations in calcium molarily has been demonstrated. 2 regular medium batches were compared with a special preparation of medium, devoid of calcium chloride then supplemented with a known concentration of calcium ions. Culture progress in each medium was assessed by: morphological observation, % cells expressing involucrin and proliferating cell nuclear antigen, cell attachment, growth rate and colony forming efficiency. In order to control the phenotype of cultured kera‐tinocytes, in a rcpoducible system, it is recommended that serum‐free keratinocyte medium is purchased with the omission of calcium chloride. Supplementation of this medium may then be made by the investigator to suit individual culture requi

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00243.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract4 clonal sublines of Cloudman S91 melanoma cells, S91/mel, S91/13, S91/6 and S91/amel, were evaluated for changes in growth, pigment content and plating efficiency during and after treatment with a cyclic‐AMP phosphodiesterase inhibitor‐melanin‐stimulating agent, 3‐isobutyl‐l‐methyl‐xanthine (IBMX) plus β‐melanocyte stimulating hormone (β‐MSH) or IBMX alone. After combined treatment, increases in melanin content on day 3 were 48, 27, 11, and 2 pg/cell in the four cell lines respectively. In each case IBMX alone was less effective than IBMX plus β‐MSH. Doubling time increased and plating efficiency decreased with increased melanization. The increases in doubling time and decreases in plating efficiency were cell line dependent. The greatest rate of increase in doubling time and decrease in plating efficiency as a function of melanin content were seen in S91/amel, which produced the least pigment. The lowest rates of increase/decrease were seen in S91/mel, which produced the most pigment. Melanin pigment induced in the cells was classified as etimelanin by EPR determination. The differential response to induction of pigmentation makes these cell lines suitable models for comparative studies on the role of melanin i

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00244.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractGeneralized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal form of junctional epidermolysis bullosa characterized by generalized skin and mucosal blisters that heal with atrophy; other features include alopecia, nail dystrophy, large melanocytic nevi, and autosomal recessive inheritance. The specific aim of this study was to identify an abnormality in epidermal basement membrane adhesion molecules in well characterized GABEB patients that would explain why these subjects' epidermis separates from their epidermal basement membrane. Cryostat sections of nonlesional skin from 8 GABEB patients in 5 different families as well as skin from normal volunteers (controls) were studied by indirect iminunofluorescence microscopy using rabbit antiserum directed against a BPAG1 fusion protein or monoclonal antibodies directed against the extracellular domain of BPAG2 (HD18 and 233), epiligrin (P1E1), laminin 5 (GB3), types IV and VII collagen, or integrin subunits α2, α3, β, α6, or β4. In these studies, monoclonal antibodies HD18 and 233 showed no reactivity and diminished reactivity, respectively, to the epidermal BM of all GABEB patients. Interestingly, in one patient, the absent or diminished reactivities of monoclonal anti‐BPAG2 antibodies were limited to well demarcated portions of an otherwise intact epidermal basement membrane. Moreover, BPAG1, epiligrin, laminin 5, types IV and VII collagen, and all integrin subunits under study were expressed in the same manner in both GABEB and normal human skin. These findings identify an abnormality in the extracellular domain of BPAG2 in the skin of GABEB patients. BPAG2 (type XVII collagen) is a transmembrane, hemidesmo‐some‐associated molecule whose extracellular domain resides at the exact level where blisters develop in the skin of patients with GABEB. Impairment of this adhesion molecule may play a key role in the pathogenesis of this inherited subepidermal bullo

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00245.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract87 subjects sensitive to both nickel sulfate and palladium‐chloride pet., were contemporaneously patch retested to nickel sulfate 5% pet., metallic palladium chloride 1% pet. and to palladium chloride 1% aq. Whilst all subjects reacted to nickel sulfate and palladium chloride pel., only 3 reacted to palladium chloride aq. No positive reactions were found to metallic palladium. The negative results to palladium chloride aq. are probably due to the formation of a new palladium ion (PdC4)2−, achieved on adding an amount of hydrocloric acid to the aqueous solution of PdCl2. The findings seem to demonstrate that the allergic reaction to palladium depends on the arrangement of the metal electrons. The sensit‐ization to palladium does not seem to be dependent on the element itself but on the complexes formed by the different compounds. The concomitant reactions to nickel and palladium ions could be dependent on the generation of similar complexes between the ions and the skin pro

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00246.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractIn order to define the influence of contact allergens on the fluid‐phase endocytosis (FPE) of soluble molecules of murine epidermal Langerhans cells (LC), we studied the internalization of FITC‐labeled bovine serum albumin (FITC‐BSA), TRITC‐labeled dextrane (TRITC‐DEX) as well as horseradish peroxidase by LC. A 3‐parameter flow‐cytometric technique was performed for quantification of internalized FITC‐BSA in LC using quantum red‐labeled reagents for detection of la‐antigen expression by LC and propidium iodide for exclusion of dead cells from analysis. A temperature‐dependent rapid accumulation of FITC‐BSA was noticed in time‐course studies reaching a plateau between 1 and 2 h ofin vitroculture at 37°C. The quantity of FPE under stimulation with phorbol 12‐myristate 13‐acetate (PMA), concanavalin A (Con A), sta‐phylococcal enterotoxin B (SEB) and contact sensitizers (DNFB, Kathon CG, K2Cr2O7) as well as the irritant SLS was determined. Treatment of LC with PMA and Con A resulted in a significant increase of total FITC‐BSA uptake. The contact sensitizers as well as SEB and SLS failed to mediate augmented fluid‐phase endocytosis. By use of the pH‐insensitive soluble marker, TRITC‐DEX and a microscope photometer for evaluation these findings could be confirmed. This excluded any artificial influence of differences in pH values in endocytotic compartments which might have influenced the fluorescence intensity of the pH‐sensitive fluoro‐chrome FITC. For qualitative analysis of FPE, the intracellular distribution of internalized horseradish peroxidase in LC was studied. An aggregated pattern became apparent in untreated LC and did not change under stimulation with any of the substances used. This was in sharp contrast to a modulation of receptor‐mediated endocytosis of antibody‐crosslinked MHC class II molecules under the influence of contact sensitizers, and suggested that haplen‐mediated endocytotic activation of LC w

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00247.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractWe measured the concentrations of total porphyrins and their metabolites (uro‐, hepta‐, hexa‐, penta‐, copro‐ and protoporphyrin) in various human tissues: liver, erythrocytes, skin, adipose tissue, and mammary gland. The porphyrin concentrations varied within minor limits, e.g., 3.1 ±2.3 nmol porphyrins/g liver and 0.50±0.10 nmol/g erythrocytes. No significant differences were detectable in other tissues in comparison with liver. In all tissues, the predominant metabolite was protoporphyrin, followed by coproporphyrin, whereas only low concentrations of higher carboxylatcd porphyrins such as uroporphyrin were detectable. It is concluded that porphyrin metabolism and its regulation is similar in all human tissues, perhaps with some small differences in the e

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00248.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe basic understanding of mast cell ontogeny and function has been fundamentally changed in recent years with observations that the cells produce and respond to a broad range of cytokines. These rapidly accruing data and their potential significance were discussed at the recent symposium “Mast Cells in the Cytokine Network”, and the overview lectures of most speakers are summarized in this special journal issue. In the present introductory manuscript, the organizers of the meeting discuss data fundamental to an understanding of the topic and highlight aspects of special interest. They consider mast cells to be defined most reliably by their unique ultrastructure since the cells are highly heterogeneous in dependence of the species studied, their tissue location, their stage of development and probably also in relation to cytokines. Most other characteristics of mast cells are shared with diverse other cell types. Murine mast cell development is induced by several cytokines. These factors are mostly ineffective in human cells except for stem cell factor which causes mast cell development from CD34+/c‐kit+ progenitors. There is however recent evidence thai fibroblasts and keratinocytes produce additional growth factors for human mast cells. Regarding cytokine secretion, most molecules known so far are produced by both murine and human mast cells. The cells furthermore bear receptors for several cytokines, enabling them to respond in an autocrine and paracrine fashion. Mast cells may thus function within a complex cytokine network, affecting physiological as well as immunological and inflammatory proc

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00249.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractThe regulation of tissue mast cell number depends both on the rate of production of mast cell precursors from bone marrow and the length of survival of mature mast cells within tissues. Mast cells develop from bone marrow under the influence of both interleukin‐3 (IL‐3) and the c‐kit ligand, also known as stem cell factor (SCF). In humans, the mast cell precursor is CD34+, FcERI‐. Mast cell precursors with time become less responsive to IL‐3 and more responsive to SCF. Mast cell proliferation directed by SCF is enhanced by other cytokines including both IL‐4 and IL‐10. Once mast cell precursors target to tissues, their survival may largely be dependent upon the local production of SCF. Withdrawal of IL‐3 or SCF results in mast cell apoptosis; SCF rescues mast cells following IL‐3 withdrawal. TGF‐beta prevents this SCF rescue. Engagement of extracellular matrix by integrin receptors may also effect mast cell numbers. Thus, in the final analysis, mast cell numbers, while relatively constant in the normal state, may be up‐regulated by altering the rate of their production centrally or length of surv

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00250.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

AbstractStudies from several laboratories have revealed that structurally diverse substances including the wasp venom, mastoparan (MP), activate purified regulatory heterotrimeric guanine nucleotidc‐binding proteins (G‐proteins) in a receptor‐independent manner, presumably by mimicking the effects of heptahelical receptors. Mast cells and differentiated HL‐60 human leukemic cells are useful model systems for the analysis of receptor‐independent G‐protein activation. We compared the effects of 2‐phenylhistamines which are cationic‐amphiphilic, too, and of MP on G‐protein activation in dibutyryl cAMP‐differentiated HL‐60 cells and in the rat basophilic leukemia cell line, RBL 2H3. In HL‐60 cells, 2‐phenylhistamines show stimulatory effects which resemble those of formyl peptide receptor agonists but which cannot be attributed to agonism at classical receptors. 2‐phenylhistamines do not, however, activate RBL 2H3 cells and various other myeloid cell types, pointing to cell type‐specificity of receptor‐independent G‐protein activation. In HL‐60 cells, MP shows effects on G‐protein activation which differ substantially from those of formyl peptides. In RBL 2H3 membranes, MP shows similar effects on G‐prolein activation as in HL‐60 membranes. We develop a model according to which receptor‐independent G‐protein activation can be subdivided into direct and indirect receptor‐independent G‐protein activation. In case of the former mechanism, substances like 2‐phenylhislamines interact with G‐protein α‐subunits and in case of the latter mechanism, substances like MP interact with nucleoside diphosphate kinase which catalyzes the formation of GTP. This newly formed GTP is then transferred to, and cleaved by, G‐protein a‐subunits. NDPK is a novel target for the design of drugs which interfere with G‐protein‐mcdiated signal transduction at a post‐receptor level and ma

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1995.tb00251.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY