Search

Mast cells are traditionally viewed as effector cells of allergic reactions and parasitic diseases, but their importance in host defense against bacteria, in tissue remodelling, their bone marrow and stem cell origin and a central role of the stem cell factor (SCF) as mast cell growth and chemotactic factor has been worked out only in recent years. Despite this, major aspects about the nature of the cells and their role in disease remain unclear. This holds in particular for the identification of mast cell precursors and the role of growth factors that stimulate specific mast cell commitment from stem cells, such as nerve growth factor, neutrotrophin-3 and certain interleukins, alone and during interaction with SCF. Early data suggesting also an involvement of specific transcription factors need to be expanded in this process. Furthermore, although mast cell proliferative disease (mastocytosis) has been shown to be often associated with SCF receptor c-kit mutations, reasons for the development of this disease remain unclear. This holds also for mast cell release mechanisms in many types of mast cell-dependent urticaria. Exciting new insights are emerging regarding the role of mast cells in bacterial infections, in defense against tumors, in wound healing and in the interplay with the nervous system, with hormones, and in the neurohormonal network. The aim of this reflection is to delineate the many known and unknown aspects of mast cells, with a special focus on their development, and to discuss in detail two mast cell-related diseases, namely mastocytosis and urticaria. [ABSTRACT FROM AUTHOR]

Background: Little is known about the involvement of B cells in venom immunotherapy (VIT). To elucidate changes in the B cell phenotype during this process, we examined the expression of several surface molecules on peripheral B cells before and during VIT. Methods: 15 venom-allergic patients with a history of systemic reactions after a wasp sting and venom-specific skin test reactivity as well as serum IgE were investigated before VIT (day 1), 1 day after reaching a maintenance dose of 100 μg (day 6) during inpatient rush VIT, and again on day 26 during continued outpatient maintenance therapy. Changes in the serum levels of total IgE, allergen-specific IgE (sIgE) and sIgG4 were measured by ELISA. Expression of several surface molecules on double-labelled B cells was studied by flow cytometry of peripheral blood mononuclear cells. Results: Levels of total IgE, sIgE and sIgG4 showed a significant increase after 26 days of VIT. On day 6, cell surface expression of HLA- II-DR, CD5, CD32 and CD54 was decreased in intensity and numbers of positive cells compared to day 1, while on day 26, expression of these molecules approached again baseline levels. Furthermore, a trend to decreased CD23 was noted on day 6. No changes were observed for CD40, CD86, CD95 and HLA-I-ABC. Conclusion: These data show that during initiation of rush VIT, B cell expression of surface molecules involved in T-B cell cooperation and antigen presentation is downmodulated. B cells may thus be additional direct or indirect targets of high-dose antigen therapy and contribute to the persistence of TH1 responses during maintenance VIT treatment.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cutaneous mastocytosis (CM) encompasses several distinct patterns of disease which can be distinguished by the type of skin lesions, age of onset, familial occurrence, noncutaneous involvement, associated c-kit mutations, and prognosis. A clear distinction of the type of CM in individual patients has important implications regarding patient management and prognosis.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In order to examine the diagnostic value of systemic provocation tests, we studied 56 inpatients hospitalized for identification of the agent eliciting previous severe allergic or pseudoallergic reactions to non-steroidal anti-inflammatory drugs, local anaesthetics or antibiotics. Skin tests were positive in only 4 patients reacting to antibiotics and propyphenazone and were always negative for local anaesthetics (n=32). Only 4 of 26 patients reacted to oral or subcutaneous provocation, 3 times to penicillin and once each to mepivacain, propyphenazone and cyanocobalamine when the suspected drug was tested. In the remaining 30 patients, who for safety reasons were tested only with alternative drugs, none had positive reactions, but 11 patients reported non-specific symptoms, as did 9 of 21 patients given placebo. Systemic provocation tests for drug allergy thus gave few positive results. However, these tests should always be done together with placebo testing for validation of results, and they remain indispensable for identification of alternative, well-tolerated drugs. [ABSTRACT FROM AUTHOR]

In order to clarify the pathomechanisms of fleeting versus more persistent wheals, expression of endothelial adhesion molecules was studied in biopsies of lesional and uninvolved skin of 15 patients with different types of whealing reactions, using immunohistochemistry. In wheals of ⩽ 30 min duration, no increase of ELAM-1 and ICAM-1 was noted. GMP-140 expression was absent in prick tests, but could be demonstrated in lesions of cholinergic and cold urticaria, with a gradual increase of the latter with time. In wheals of ⩾ 6 h duration, GMP-140 was only weakly expressed whereas ELAM-1 and ICAM-1 were markedly up-regulated in lesional and less so in nonlesional skin of acute, chronic recurrent and delayed pressure urticaria. This differential expression of endothelial adhesion molecules may reflect the activity of mast cell-derived and other mediators during the elicitation phase and explains the persistence of wheals in different types of urticaria. [ABSTRACT FROM AUTHOR]

Since mast cells and basophils are thought to play a central role in several types of cutaneous inflammatory and allergic reactions and since interleukin-6 (IL-6) is an important mediator in these processes, we have studied the ability of the human mast cell line HMC-1, the human basophilic cell line KU812 and human skin mast cells to produce IL-6. All three cell types proved to be potent sources of this cytokine after appropriate stimulation. Transcription of IL-6 mRNA was first detectable 2 h after stimulation with the ester phorbol myristate acetate (PMA) and the calcium ionophore A23187 in both cell lines, as evidenced by semiquantitative reverse transcriptase polymerase chain reaction analysis. Whereas resting cells did not produce IL-6 protein, PMA/A23187- stimulated cells released immunoreactive and biologically active IL-6, as demonstrated and quantitated by enzyme-linked immunosorbent assay and by the use of TEPC 1033 cells an IL-6-dependent murine plasmacytoma cell line. Stimulated KU812 cells secreted sevenfold more IL-6 (up to 15 ng/ml) than HMC-1 cells (up to 2.4 ng/ml). Immunoblotting of HMC-1- and KU812 cell-derived IL-6 revealed several IL-6 forms in the molecular weight range of 2l to 30 kDa. Immunoelectron microscopic studies of human skin biopsies provided evidence that unstimulated mast cells do not contain preformed IL-6 but accumulate IL-6 in cytoplasmic and extruded granules after IgE-dependent stimulation. These findings suggest that IL-6 secreted by human mast cells and basophils potentially contributes to allergic, other immunologically mediated and nonspecific inflammatory responses. [ABSTRACT FROM AUTHOR]