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J Grabbe

Publications and source records attributed to J Grabbe.

At least 55 records · Page 3Linked to original sources
PubMed1997

More positive patch test reactions with larger test chambers? Results from a study group of the German Contact Dermatitis Research Group (DKG).

Test chambers of various sizes are commercially available for patch testing. Therefore, we asked the question whether the size of patch test chambers may affect allergic patch test reactions. A total of 495 patients were double tested synchronously with small and large Finn Chambers containing standard preparations of fragrance mix, wool wax alcohols, Kathon CG and formaldehyde. Double tests in 217 patients who had reacted with at least 1 allergic, questionable, or irritant reaction to 1 of these allergens were statistically evaluated. For each of the 4 allergens, a significantly higher number of stronger reactions was seen with the large chambers as compared to the small ones. It is concluded that large test chambers may be useful for detection of weak sensitizations to particular contact allergens.

Adult↗
PubMed1996

Release of stem cell factor from a human keratinocyte line, HaCaT, is increased in differentiating versus proliferating cells.

Stem cell factor, a recently discovered growth factor for hematopoietic stem cells, mast cells, and melanocytes, was initially reported to be produced by fibroblasts. In this study, we investigated the secretion of this factor from human HaCaT cells during in vitro culture and compared it to synthesis by cells in the skin. Release of stem cell factor from freshly cultured keratinocytes was comparable to that of HaCaT cells and was nearly half that produced by fibroblasts and umbilical vein endothelial cells. No stem cell factor was detectable in culture supernatants of melanocytes. HaCaT cells underwent spontaneous differentiation after a period of proliferation until confluency. Depending on duration of culture, they released increasing amounts of stem cell factor (approximately 150 pg/10(6) cells on day 3 (proliferating cells) vs approximately 450 pg/10(6) cells on day 14 (differentiating cells) measured by enzyme-linked immunosorbent assay. Stimulation for 24 h with the calcium ionophore A 23187 (10(-6) to 10(-8) M) further enhanced release. Western blot analysis of HaCaT cell lysates with a stem cell factor antibody revealed two proteins with the known molecular weights of membrane-bound and soluble stem cell factor. By semiquantitative reverse transcriptase polymerase chain reaction, full-length as well as spliced type stem cell factor mRNA was found to be increased in differentiating versus proliferating HaCaT cells. Keratinocytes are thus potentially important sources of stem cell factor in human skin, and HaCaT cells provide a useful model for further studies of stem cell factor from keratinocytes.

Base Sequence↗
PubMed1996

High-dose ultraviolet A1 (UVA1), but not UVA/UVB therapy, decreases IgE-binding cells in lesional skin of patients with atopic eczema.

In order to further elucidate the mechanisms by which high-dose ultraviolet A1 (UVA1) therapy leads to improvement in patients with atopic eczema, we assessed skin sections from patients before and after high-dose UVA1 therapy (n = 5) or conventional UVA/UVB therapy (n = 4) for changes in Langerhans cells and mast cells expressing the high-affinity IgE receptor Fc epsilon RI and in surface-bound IgE by histochemical and immunohistochemical techniques. The two treatment groups exhibited different patterns of changes in the number of Fc epsilon RI+, CD1a+, and mast cells within the dermis: The density of both Langerhans cells and mast cells was decreased after high-dose UVA1 therapy, but not after UVA/UVB therapy. High-dose UVA1 and UVA/UVB therapy significantly increased the number of CD1a+ cells within the epidermis, but only high-dose UVA1 reduced the relative number of IgE+ intraepidermal Langerhans cells typically found in atopic eczema. Reduction of numbers of dermal Langerhans cells and mast cells, as well as relative numbers of intraepidermal IgE+ Langerhans cells, was closely linked to significant clinical improvement by high-dose UVA1, but not UVA/UVB therapy. These studies support the notion that IgE-binding cutaneous cells are involved in the pathogenesis of atopic eczema. We propose that UVA1 radiation exerts its effects in atopic eczema, at least in part, by inhibiting Langerhans cell migration out of the epidermis and, in particular, by reducing the number of IgE-bearing Langerhans cells and mast cells in the dermis.

Cell Count↗
PubMed1996

Absence of MHC class II antigen on mast cells at sites of inflammation in human skin.

Since the presence of major histocompatibility complex (MHC) antigens has recently been reported on murine and human mast cells under various conditions, we have investigated their expression on mast cells in different types of cutaneous inflammation. Cryostat sections from lesional biopsies of patients with psoriasis, atopic eczema, chronic urticaria, lichen planus, bullous pemphigoid and urticaria pigmentosa were immunohistochemically stained with monoclonal antibodies against MHC class I and class II antigens using a double staining APAAP/toluidine blue methodology. While strongly positive staining with the antibody directed against MHC class I antigens was found on nearly all mast cells in normal skin and in inflammatory dermatoses, reactivity for HLA-DR and HLA-DQ antigens on mast cells could not be detected, except for less than 2% of cells with doubtful staining. Human mast cells therefore probably play no significant rôle as antigen-presenting cells in the conditions studied.

Antibodies, Monoclonal↗
PubMed1996

MHC class II antigen expression is increased in different forms of urticaria.

Urticarial reactions encompass a variety of inflammatory and immunological reactions. In order to clarify specific aspects of these processes, we analyzed the distribution and sequential expression of major histocompatibility complex II (MHC class II) molecules in tissue sections from different types of whealing reactions. Using immunohistochemical techniques and monoclonal antibodies, expression of HLA-DR, HLA-DP, and HLA-DQ was examined on resident and infiltrating cells in different skin cell compartments, comparing early with longer-lasting wheals and lesional with uninvolved skin. Sequential biopsies were studied in cold urticaria (CU). No increase of MHC class II molecule expression was found in early prick test wheals to common inhalant allergens. In CU, however, sequential biopsies demonstrated an up-regulation of MHC class II molecules within 30 min after elicitation. This was more pronounced in longer-lasting urticaria lesions of acute, chronic recurrent and delayed pressure urticaria, with HLA-DR and, to a lesser degree, HLA-DP and HLA-DQ being noted on cell infiltrates, on vascular endothelia and around nerves and sweat glands. Nonelesional skin in these types of urticaria also showed increased MHC class II expression. Longer-lasting urticarial wheals are thus associated with up-regulation of MHC class II molecules on resident and infiltrating cells, suggesting an involvement of these molecules in the pathomechanisms of these types of urticarial lesions.

Acute Disease↗
PubMed1995

Phenotypic characterization of skin lesions in urticaria pigmentosa and mastocytomas.

In order to identify possible cellular abnormalities in human mastocytosis, sections from 13 urticaria pigmentosa lesions and 5 mastocytomas were compared with 5 normal skin specimens using histochemical, enzyme histochemical and immunohistochemical techniques. All toluidine blue-positive mast cells also reacted with Fc epsilon RI and c-kit antibodies, almost all stained for tryptase, many for chymase and the myeloid workshop mast cell antibodies, few for Fc epsilon RII and none for the proliferation marker Ki-67. Urticaria pigmentosa lesions contained fewer epidermal Langerhans cells and a lower percentage of avidin-positive mast cells than mastocytomas and normal skin. Mastocytomas exhibited generally weaker staining for mast cell markers and mostly lacked Fc epsilon RI-bound IgE on mast cells and Langerhans cells, although the receptor was able to bind IgE in tissue sections. Most of the mast cell antibodies also reacted with other cell types. Only toluidine blue, avidin, tryptase and chymase stains were mast cell specific. Mast cells in mastocytosis thus differed only to a minor degree from normal mast cells, although distinct pathomechanisms may play a role in urticaria pigmentosa and mastocytosis.

Adolescent↗
PubMed1995

Beta 2-integrins in different forms of urticaria.

As urticarial lesions involve tissue invasion by inflammatory cells, and as beta 2-integrins play a central part in adhesion of leucocytes to endothelia, allowing their migration into the tissues, we have explored the distribution and sequential expression of these molecules in tissue sections from different forms of urticaria. Prick test weals (of 10 min duration) to common inhalant allergens showed only a minor increase of CD18, whereas in a case of cold urticaria CD11b and CD18 molecules were increasingly upregulated within the first 30 min after elicitation of the lesions. Skin test sites in delayed pressure urticaria, and urticarial lesions (> 6 h duration) of acute and chronic recurrent urticaria also showed marked upregulation of CD11b and CD18, and to a lesser extent of CD11a, but this did not strongly correlate with the intensity of the mixed cellular infiltrate. Non-lesional skin showed expression of beta 2-integrins in chronic urticaria, delayed pressure urticaria, and less so in acute urticaria, suggesting generalized leucocyte activation. This analysis of integrins thus suggests an early and extensive involvement of these molecules in the pathological events associated with the evolution of urticarial lesions.

Acute Disease↗
PubMed1995

Expression of stem cell factor in cutaneous mastocytosis.

Stem cell factor has recently been identified as a potent growth factor for bone marrow stem cells, melanocytes and mast cells. In order to evaluate its possible role in human mastocytosis, skin lesions from 13 patients with urticaria pigmentosa and five patients with mastocytomas, and normal skin specimens from five healthy donors were studied by immunohistochemistry, using polyclonal and monoclonal (hkl-12) antibodies against stem cell factor, and a monoclonal antibody (YB5.B8) against its receptor, the c-kit proto-oncogene product. Stem cell factor expression was noted in all sections studied, with an equal distribution pattern for both antibodies, but a weaker intensity with the hkl-12 reagent. Cytoplasmic staining was noted in keratinocytes, Langerhans cells, sweat gland ductal lining cells, mast cells, endothelial cells and spindle-shaped dermal stromal cells. An intense, diffusely granular reaction pattern was noted in all cells, except for a sparse, coarsely granular pattern in mast cells and stromal cells. In urticaria pigmentosa, staining was weaker in keratinocytes, but more prominent in Langerhans cells. In all sections, toluidine blue-positive mast cells and TA 99-positive basal epidermal melanocytes were the only cells to react with the c-kit antibody. Mastocytomas and urticaria pigmentosa lesions thus exhibit different patterns of stem cell factor expression. However, a possible pathogenetic role of this factor in mastocytosis remains to be determined.

Adolescent↗
PubMed1995

Two novel mast cell phenotypic markers, monoclonal antibodies Ki-MC1 and Ki-M1P, identify distinct mast cell subtypes.

In order to identify more specific or selective mast cell markers, the reactivity of two monoclonal antibodies, Ki-MC1 and Ki-M1P, was studied by immunohistochemistry in two human cell lines (mast cell line HMC-1, basophilic cell line KU812), in mast cells cultured from blood precursors, in adherent mononuclear cells from peripheral blood, and in mast cells of tissue sections from 13 urticaria pigmentosa lesions, five mastocytomas and five normal skin specimens. Toluidine blue staining, fluorescence staining with FITC-conjugated avidin, and immunohistochemical staining (APAAP) with other mast cell reactive monoclonal antibodies, was performed for comparison. Double staining with the APAAP method, using the Ki-antibodies and toluidine blue, was also carried out. Both Ki-antibodies showed reactivity for skin mast cells, but with a different staining pattern. In addition, the Ki-MC1 antibody did not react with the cell lines, and reacted only with a few peripheral blood mononuclear cells and cultured mast cells. In contrast, the Ki-M1P antibody reacted with almost all cultured mast cells and blood mononuclear cells, but stained only about one-half of lesional and one-fifth of normal skin mast cells. Ki-M1P also reacted with many toluidine blue-negative dermal cells, particularly in urticaria pigmentosa. Ki-MC1 antibody can thus be considered as a useful additional marker for normal skin mast cells. In contrast, the Ki-M1P antibody primarily identifies immature mast cells and monocytes/macrophages, suggesting that these cell types probably originate from the same bone marrow precursor.

Adult↗
PubMed1995

Expression of the c-kit receptor in hypomelanosis: a comparative study between piebaldism, naevus depigmentosus and vitiligo.

In order to investigate possible alterations in c-kit protein expression on epidermal melanocytes in different hypopigmentary disorders, we have examined skin specimens from one patient with piebaldism, one patient with naevus depigmentosus, and five patients with vitiligo. Cryosections were examined by immunohistochemistry using monoclonal antibodies against the c-kit protein (YB5.B8) and melanosomes (TA99). In piebaldism, hypomelanotic epidermis contained only a few TA99-positive epidermal melanocytes and no detectable c-kit protein, whereas in naevus depigmentosus the expression of c-kit protein was strong, and TA99 immunoreactivity was faint. In vitiligo lesions, no epidermal immunoreactivity for melanosomes or c-kit protein was found. Normally pigmented skin of all patients showed immunoreactivity of epidermal melanocytes for both c-kit protein and melanosomes. Different hypomelanotic lesions can thus be differentiated by absent melanocyte c-kit protein and low or no expression of melanosomal marker in piebaldism, normal c-kit but low melanosome expression in naevus depigmentosus, and the absence of all melanocyte markers in vitiligo.

Adult↗
PubMed1995

Mast cells.

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Animals↗
PubMed1995

Mast cells in the cytokine network: the what, where from and what for.

The 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 that 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 processes.

Animals↗
PubMed1995

Urticarial vasculitis syndrome effectively treated with dapsone and pentoxifylline.

Urticarial vasculitis is difficult to treat. We report here on a 40-year-old woman with a 16-year history of idiopathic hypocomplementemic urticarial vasculitis syndrome. Her disease had been resistant to treatment with H1- and H2-blockers, indomethacin, dapsone and interferon alpha but responded to > 25 mg/day prednisolone. Monotherapy with pentoxifylline was also of only minor benefit. Using a combination of dapsone (100 mg/day) and pentoxifylline (1,200 mg/day), we observed a gradual improvement resulting in a complete remission within 8 weeks. Complete control of symptoms could be maintained for 18 months without any serious side-effects. This type of treatment may be of benefit in other therapy-resistant cases of hypocomplementemic urticarial vasculitis syndrome, particularly in view of its excellent tolerance.

Adult↗
PubMed1994

Stem cell factor, a novel cutaneous growth factor for mast cells and melanocytes.

Mechanisms affecting mast cell and melanocyte growth and function are still poorly understood. This report summarizes the current state of knowledge on a recently described growth factor for both these cell types and for primitive haematopoietic stem cells. Stem cell factor (SCF), also named mast cell growth factor or kit-ligand, has only recently been cloned and has been shown to be encoded on human chromosome 12. It may be of specific importance in cutaneous physiology and pathology since it is produced by several cell types in the skin (e.g. fibroblasts, keratinocytes, endothelial cells) and since it affects melanocyte and mast cell growth, survival, secretion and adhesion as well as migration into tissues. Defects in the genes encoding for the SCF receptor (c-kit-protein) have been shown to be responsible for human piebaldism. A pathogenetic role in mastocytosis has recently been proposed, but remains to be proven. SCF receptor expression is decreased on cells of some malignant cell lines compared to their physiological counterparts, making it unlikely that SCF is a key factor in malignant transformation and cellular hyperproliferation. In haematopoiesis, SCF acts primarily in concert with other growth factors, and we show here that alone in serum-free culture it has no effect on mast cell growth. Furthermore, there is evidence that besides SCF, additional mast cell growth factors are secreted by fibroblasts and keratinocytes, suggesting a complex orchestration of several growth factors in the regulation of cutaneous growth and differentiation in which SCF plays only one part.

Animals↗
PubMed1994

Phenotypic evaluation of cultured human mast and basophilic cells and of normal human skin mast cells.

In order to evaluate various markers for human mast cells, two human mast/basophilic cell lines (HMC-1/KU812), cultured mast cells from the peripheral blood monocytic fraction and peripheral blood monocytes were compared with mast cells in tissue sections from normal skin, using histochemistry, enzyme histochemistry and immunohistochemistry. All reagents stained normal skin mast cells, with toluidine blue, tryptase reactivity and antibodies against the Fc epsilon RI and the stem cell factor receptor (c-kit) being most active. The cell lines and mast cells cultured from peripheral blood were negative for avidin, safranin and chymase, strongly positive for c-kit and variably reactive with all other reagents. All antibodies except AA1 against tryptase also stained one or several epidermal and dermal cell types or blood monocytes. Histochemical stains (toluidine blue, avidin) and reagents for the enzymes tryptase and chymase are thus specific markers for mast cells. The frequent reactivity of antibodies against mast cells with other cell types indicates interesting functional and ontogenetic relationships between these cells.

Antibodies, Monoclonal↗
PubMed1994

Comparative cytokine release from human monocytes, monocyte-derived immature mast cells, and a human mast cell line (HMC-1).

To obtain further information regarding the role of cytokines during mast cell differentiation, we have investigated changes of cytokine secretion in mast cells developing from the human peripheral blood monocytic cell fraction during culture with fibroblast-derived conditioned media. The influence of stem cell factor and an antibody to the respective receptor in our culture system was studied as well. Interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)alpha were spontaneously secreted by cultured cells at day 1 and decreased markedly by day 14. Similar changes occurred also during culture with stem cell factor and were partially abrogated by an anti-receptor antibody. IL-8 was secreted at a high level throughout the culture, whereas no spontaneous secretion of IL-2, IL-3, IL-4, and IL-7 was measured at all. Upon stimulation with phorbol myristate acetate and A23187, cultured cells showed substantially more release of IL-3 and TNF-alpha after 14 d of culture, compared to peripheral blood monocytic cells. Preformed TNF-alpha was found in one of three monocytic cell preparations from peripheral blood, but not in monocytic cell-derived mast cells. During mast cell differentiation, cytokines from monocytic cells are therefore downregulated while the cells assume a pattern typically found in mast cells.

Cell Line↗