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Biomedical subjects

J Grabbe

Publications and source records attributed to J Grabbe.

At least 73 records · Page 4Linked to original sources

Foreign-body granuloma and IgE-pseudolymphoma after multiple bee stings.

We report a patient with an unusual combination of an eosinophilic foreign-body granuloma and a pseudolymphoma, with recurrent severe oedema on the forehead, after multiple bee stings. On immunohistology the foreign-body granuloma and lymphoid follicles reacted with monoclonal antibodies against the high- and low-affinity IgE receptors, and against IgE. Prick and intradermal tests with whole-body bee extracts showed positive immediate-type reactions. The eosinophilic granuloma formation and lymphoid follicles may have been induced by a combination of immune complex and cell-mediated hypersensitivity following antigen persistence. Although bee stings are common, as far as we are aware, this complex reaction pattern has not been reported previously.

Animals↗

[The mast cell].

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Humans↗

[The mast cell].

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Basophils↗

Demonstration of the high-affinity IgE receptor on human Langerhans cells in normal and diseased skin.

Epidermal dendritic cells of normal adult foreskin, and of lesional skin from patients with atopic eczema, stasis eczema and urticaria pigmentosa are shown to be highly reactive with two different monoclonal antibodies (29C6 and 6F7) specific for extracellular domains of the alpha-chain of the high-affinity IgE receptor. By their distribution pattern, the reactive cells are Langerhans cells. This is confirmed by immunoelectron microscopic demonstration of Birbeck granules in the labelled epidermal cells. Very weak staining is observed on the same cells with an antibody (Tü1) against the low-affinity IgE receptor. Pre-incubation of the sections with IgE partially blocks binding of 6F7 antibody. Langerhans cells, together with dermal mast cells, can therefore bind IgE with high efficiency, and may in this way participate in IgE-mediated cutaneous diseases.

Adult↗

Demonstration of the high-affinity IgE receptor (Fc epsilon RI) on Langerhans cells of oral mucosa.

Langerhans cells in the skin have recently been shown to bind IgE molecules via a high-affinity IgE receptor. Using two specific antibodies, 29C6 and 6F7, against the alpha-chain of the high-affinity IgE receptor, we here demonstrate that Langerhans cells express this receptor in oral mucosa. A specific antibody, Tü1, against the low-affinity IgE receptor showed only low expression of this receptor. High-affinity binding for IgE may be important for induction and support of Langerhans cell-dependent transepithelial IgE-mediated allergic reactions and inflammation.

Antibodies, Monoclonal↗

Skin prick tests to common allergens in adult atopic eczema and rhinitis patients: reproducibility on duplicate and repeated testing.

Skin prick test reactivity to a battery of common allergens was examined in 26 adults with atopic eczema, in 9 patients with allergic rhinitis and in 10 nonatopic controls. In both patient groups, reactivity was most frequent for grass pollen, followed by rye, house dust mite, tree and herb, with no reactions to food allergens. Repeated tests at weekly intervals were less reproducible in weak reactions and in severely affected eczema patients compared to those lightly affected. Skin prick tests are therefore reliable and reproducible in atopics and provide means to counsel patients on avoidance of eliciting agents of their disease.

Adult↗

[Lymphoplasmocytoid immunocytoma of the skin].

A 68-year-old male patient presented with numerous red-brown papules on the trunk and neck. Cutaneous lymphoplasmocytoid immunocytoma was diagnosed following histological and electron microscopical detection of atypical lymphoid cells in the dermis. Immunohistochemistry revealed a monoclonal proliferation of IgG-kappa-positive B-lymphocytes. There was no extracutaneous manifestation of the lymphoma. Complete remission was affected by total-body irradiation with an electron beam.

Biomarkers, Tumor↗

Expression of the high affinity IgE-receptor on human Langerhans' cells. Elucidating the role of epidermal IgE in atopic eczema.

Epidermal Langerhans' cells have previously been shown to bear IgE molecules, particularly in atopic dermatitis skin. Using two highly specific antibodies against the antibody-binding chain of the high affinity IgE-receptor, 29C6 and 6F7, we here provide evidence that Langerhans' cells express this receptor in both normal skin (foreskin) and in lesional skin of patients with atopic and stasis eczema. A specific antibody against the low affinity IgE-receptor, Tü1, showed only a low expression of this receptor. This finding has important potential functional implications for the role of Langerhans' cells in transepidermal, IgE-mediated allergy.

Antibody Affinity↗

Cutaneous toxicity of high-dose carboplatin, etoposide and ifosfamide followed by autologous stem cell reinfusion.

Forty patients with germ cell tumors were treated with carboplatin 1500-2000 mg/m2, etoposide 1200-1600 mg/m2 and ifosfamide 0-10 g/m2 plus mesna followed by autologous stem cell reinfusion. A pruritic maculopapular rash was observed in 10 patients usually starting on the last day of chemotherapy. Lesions remained localized to the extremities in four patients. In six they became confluent and progressed also involving the trunk and face. Facial edema and painful swelling of hands and feet also occurred in this latter group. No ulcerations or bullae formation were seen and changes resolved spontaneously in all patients within 3 weeks leaving marked hyperpigmentation in involved areas. Renal function declined in nine of 10 patients concomitantly with evolving cutaneous changes, but recovered in all except one. Cutaneous side effects were more frequent with increasing doses of etoposide and carboplatin and in patients with deteriorating renal function. Plasma concentrations during high-dose chemotherapy should be monitored to avoid excessive serum levels and toxicity, especially in patients at risk of renal dysfunction.

Antineoplastic Combined Chemotherapy Protocols↗

In vitro generation of smooth muscle-contracting leukotrienes from isolated epidermal cells.

Single-cell suspensions of murine and human epidermal cells were studied for the presence of peptidoleukotrienes (LTs), using in vitro guinea pig ileum contraction as bioassay and a commercial radioimmunoassay. The calcium ionophore A23187 at 5 x 10(-6) M alone or in combination with arachidonic acid at 10(-4) M caused release of LTC4/D4 within 10-30 min and for up to 18 h. LTB4, as was measured in the chemotaxis assay, was released at different levels and with different kinetics from the same cells. Epidermal cells may thus regulate cutaneous inflammation by secreting potent vasoactive and muscle-contracting in addition to chemotactic lipid mediators.

Animals↗

Mast cells and their mediators in immediate and delayed immune reactions.

Tissue mast cells and the closely related blood basophils are distinguished by their special mediators and their high-affinity IgE membrane receptors. These properties have made the cells be viewed traditionally as effector cells of immediate-type hypersensitivity reactions. More recently, mast cells have been shown to develop from the myeloid series of the bone marrow under the influence of interleukins 3, 4, 6, 9, 10 and 11. Mast cell and basophil lines of murine and human origin have also been shown to express and release interleukins 1, 3, 4, 5, 6, 8, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulizing factor and interferon-gamma. Certain cytokines are also able to induce mediator release from mast cells. Furthermore, mast cells have in the past been shown to be modestly phagocytic and to express major histocompatibility complex class II membrane markers after appropriate stimulation. These findings show that mast cells are intricately associated with immune reactions and suggest that they may not only sustain and modulate but possibly also initiate immune responses.

Animals↗

Detection of native human complement components C3 and C5 and their primary activation peptides C3a and C5a (anaphylatoxic peptides) by ELISAs with monoclonal antibodies.

Monoclonal antibodies (mAbs) were raised against human C3a, C3b, C5a, and C5b after immunization of BALB/c mice with the native components C3 and C5. Using different combinations of these mAbs we have developed four sensitive sandwhich-enzyme-linked immunosorbent assays (ELISAs) for the detection of native C3 or C5 in samples with low concentrations of these proteins, e.g., in cell culture supernatants or synovial fluids and cerebrospinal fluids (CSF) and for the detection of the anaphylatoxic peptides (AT-peptides) C3a or C5a in human EDTA-plasma. The C3- and C5-ELISAs were found to be specific for the uncleaved complement proteins. Two different anti-C3a or anti-C5a mAbs were combined for the C3a- and C5a-ELISA. Before assaying a sample in the C3a- or C5a-ELISA a precipitation step to eliminate uncleaved C3 and C5 was necessary. The sensitivity and specificity of the four ELISAs were tested with purified antigens and EDTA-plasma or Cobra venom factor-activated EGTA-plasma samples as a source of C3a and C5a. The detection limits were 1 ng/ml for C3, 1 ng/ml for C3a, 2 ng/ml for C5, and 100 pg/ml for C5a. Plasma samples from patients undergoing cardiopulmonary bypass (CPB) surgery were used as a source of pathological material.

Anaphylaxis↗

Production of LTB4-like chemotactic arachidonate metabolites from human keratinocytes.

Keratinocytes have recently been recognized as a source of mediators of cellular immune function. We present here further data on the production of 5-lipoxygenase-dependent arachidonate metabolites from freshly isolated human epidermal cells. Stimulation of cells with arachidonic acid or the calcium ionophore A 23187 alone or together caused a dose- and time-dependent release of chemotactic activity which was maximal during the first 10 min and which continued for up to 18 h. Indomethacin (10(-6) M) enhanced and compound BW 755C (20 micrograms/ml), a lipoxygenase inhibitor, decreased release. The chemotactic activity was heat stable for 30 min at 56 degrees C and was extractable into ether at pH 3.0. Analysis of 15- and 30-min supernatants showed coelution of biologic activity and of leukotriene B4 (LTB4), as measured by radioimmunoassay, at marker positions of LTB4 and of 20-OH-LTB4. Elimination of Langerhans cells did not alter the secretion of chemotactic lipids, suggesting that keratinocytes are the main source of potent, biologically active, lipoxygenase-dependent arachidonate metabolites.

Arachidonic Acids↗

Generation of leukotrienes from normal epidermis and their demonstration in cutaneous disease.

In order to evaluate the significance of chemotactic leukotrienes in cutaneous disease, synthetic leukotriene B4 and its metabolites were examined during in vitro chemotaxis. Leukotriene B4, and less so 20-OH-leukotriene B4, were chemotactic for neutrophils and eosinophils, with a preferential attraction of eosinophils. The responsiveness of human monocytes towards leukotriene B4 was relatively low. Normal cells and cells from different patients varied in their quantitative response. Cells from patients with eczema and T-cell lymphoma tended to migrate less than those from patients with other inflammatory diseases. Leukotrienes are generated from several types of peripheral leukocytes. In order to examine whether resident cells of the skin can also produce these factors, isolated human and murine epidermal cells were examined for their ability to generate leukotriene B4 and leukotriene C4 in vitro. Arachidonic acid, and less so the ionophore A 23187, induced the generation of both types of factors, based on the finding in the bioassay, reverse-phase high-pressure liquid chromatography and radioimmunoassays. The same factors were demonstrated by either or all of these methods in skin biopsies, scales, blisters or suction blisters of patients with psoriasis, pitysiasis rubra pilaris, dyshidrosis, bullous pemphigoid, pressure urticaria, urticaria pigmentosa and drug reactions, but not in Sézary syndrome nor in callus and skin biopsies of normal controls. These findings underline the fact that the leukotrienes are potent inflammatory mediators in diverse skin diseases, but that they are not limited to any specific disease. Furthermore, a relationship between leukotrienes and tissue eosinophilia does not exist.

Animals↗