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  • 1
    Electronic Resource
    Electronic Resource
    Quantitative analysis of tryptase- and chymase-containing mast cells in atopic dermatitis and nummular eczema (1997)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 136 (1997), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The distribution of mast cells (MCs) containing tryptase (T) and chymase (C) was studied in the non-lesional and lesional skin of 26 patients with atopic dertnatitis (AD) and 23 patients with non-atopic nummular eczema (NE). and in the skin of eight healthy controls. T and C activities were demonstrated enzymehistochemically using 2-Gly-Pro-Arg-MNA and Suc-Val-Pro-Phe-MNA as substrates, respectively. The T- and C-containing MCs were counted separately in the epidermis, in contact with the basement membrane. In the papillary dermis and in different dermal levels (0·2 mm each). Also, the C protein was determined immunohistochemically. T-positive MCs were similarly distributed in non-lesional and lesional skin of both AD and NE. The MC number was relatively high in the upper dermis (papillary dermis and levels I and I!) of non-lesional and lesional skin of AD. In the upper dermis of non-lesional AD and NE skin and in normal skin, about 50% of T-positive MCs displayed C activity, whereas the percentage in lesional AD and NE skin was only about 30%. hi this respect, the non-lesional and lesional samples differed significantly froLu each other in both dennatoses (in AD p = 0%005, in NEP = 0·002. Students' t-test). In all samples the MC number decreased in the deeper dermal levels, although numerous T-containing MCs were still counted in the deeper dermis (dermal levels IV-VII) of lesional AD and NE skiti. differing significantly from the MC number in normal skin (In ADp = 0·005. in NE p=0·041). In the deeper dermis. the percentage of MCs containing active C was about 70% in non-lesional and lesional AD and NE. and about 90% in normal healthy skin. However, in the upper dermis of non-lesional and lesional skin of both AD and NE. about H()% of all MCs contained the C protein, which differed significantly from the value of 100% in normal skin (p〈0·5). In conclusion, the increased number of T-positive MCs in the upper dermis of non-lesional and lesional AD contributes to promoting inflammation. C apparently loses its activity in the upper dermis of lesional AD and especially in NE. Thus. Ihe enzyme partially lacks its capability to suppress inflammation, such as degradation of neuropeptides and proteins. The dysregulation of these proteinases exists already in non-lesional skin of AD and NE.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.1997.01831.x
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  • 2
    Electronic Resource
    Electronic Resource
    The release of histamine is associated with the inactivation of mast cell chymase during immediate allergic wheal reaction in the skin (2001)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 31 (2001), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Chymase released by mast cells can participate in the immediate allergic wheal. However, chymase may be susceptible to inactivation by protease inhibitors during degranulation.Objective To study the inactivation of chymase and the release of histamine in the immediate allergic wheal reaction.Methods Ten sensitive atopic subjects were prick-tested with the cow dander allergen, and skin biopsies were taken from the control skin and from the challenge site at 30 and 120 min. Tryptase (Tact) and chymase (Cact) activities in mast cells were measured enzyme-histochemically. Sequential double-staining was used to demonstrate the activity and immunoreactivity (Cprot) of chymase in the same mast cell as well as α1-proteinase inhibitor (α1-PI) and α1-antichymotrypsin (α1-AC) in Tact+ cells. Skin microdialysis was used to monitor histamine release after the allergen challenge for up to 120 minResults The numbers of Tact+ and Cact+ cells were already maximally decreased at 30 min by 37 ± 17% and 61 ± 31%, respectively (mean ± SD, P 〈 0.0001). At the same time the Cact+/Cprot+ ratio decreased from 82 ± 15% to 43 ± 16% (P 〈 0.0001). The cumulative histamine release at 30 min correlated negatively with the Cact+/Tact+ (P = 0.047) and Cact+/Cprot+ (P = 0.024) ratios, but positively with the decrease in the number of Cact+ cells (P = 0.024). These data indicate that the higher the histamine release the lower the chymase activity. Also the number of Tact+ cells in the control skin correlated positively with the cumulative histamine release at 120 min (P = 0.043). In the control skin, 95 ± 6% and 76 ± 8% of the Tact+ cells displayed α1-AC and α1-PI, respectively.Conclusion In addition to extensive degranulation of mast cells, chymase is also rapidly inactivated after the allergen challenge, possibly by pre-existing chymase inhibitors in the mast cells. This inactivation is associated with the release of histamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2001.01030.x
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  • 3
    Electronic Resource
    Electronic Resource
    Release of soluble tryptase but only minor amounts of chymase activity from cutaneous mast cells (2001)
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 10 (2001), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Tryptase and chymase are the major serine proteinases of skin mast cells but their biologic significance depends on their activity. In this study, we demonstrate the release of soluble activity of tryptase, but not markedly that of chymase, into skin blister fluids induced by freezing with liquid nitrogen as well as into supernatant during incubation of 8 whole skin specimens with compound 48/80 for up to 2 days followed by sonication. Incubation of 3 other skin specimens in compound 48/80 for up to 2 days revealed that the number of mast cells displaying tryptase activity decreased significantly on day 2, and the number of mast cells showing chymase activity (but not those showing chymase immunoreactivity) decreased significantly on day 1 but not thereafter on day 2. The results of 3 skin organ cultures for up to 14 days showed steady decrease in the number of tryptase-positive cells but persistence of mast cells containing chymase activity. Chymase in solution was sensitively inhibited by 0.01 mg/ml α1-antichymotrypsin but higher concentrations (0.3–3.0 mg/ml) were needed for inhibiting chymase on skin sections. In conclusion, after mast cell degranulation tryptase activity is substantially solubilized and it may potentially affect both local and distant skin structures. Instead, chymase is partially inactivated and the remaining chymase activity persists at the site of degranulation having only local effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0625.2001.100404.x
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  • 4
    Electronic Resource
    Electronic Resource
    Histamine release in skin monitored with the microdialysis technique does not correlate with the weal size induced by cow allergen (1996)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 134 (1996), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary The purpose of this study was to monitor histamine release in immediate-type hypersensitivity reactions in the skin of 10 atopic patients, sensitive to cow, by using the microdialysis technique. Three healthy subjects, without any atopic features or background, served as the control group. The probe inserted into the forearm dermal skin was perfused with isotonic saline solution. Samples were collected at 15-min intervals. After the first allergen challenge of four prick tests close to the probe with cow allergen extract, the skin was similarly repricked again in five patients and three healthy subjects, and in five other patients, 25μl of 10μmol/l substance P (SP) was injected intracutaneously. The samples were analysed for histamine by radioenzyme assay. The patients were clinically evaluated for allergic symptoms, prick- and scratch-patch test reactivity and for serum cow-specific, and total, IgE levels.The baseline histamine concentration was 7·5±4·0 nmol/l (mean±standard deviation: SD; n=10). After the allergen challenge, the histamine concentration in the consecutive samples was 11·9±11·0 nmol/l, 91·1±127·3 nmol/l, 61·0±94·2 nmol/l and 33·7±53·7 nmol/l. The peak concentration was detected in the 15–30 min fraction, and it varied between 0 and 406 nmol/l regardless of the weal size. The second allergen challenge was unable to induce marked additional histamine release, but SP induced extensive histamine liberation in those patients who did not exhibit histamine release during the preceding prick tests. In three healthy subjects, the baseline histamine concentration was 6·2±3·9 nmol/l. After the allergen challenge, no additional histamine liberation could be measured.Surprisingly, the histamine release was not related to the size of the cow-induced weal nor was it related to any specific allergic symptoms or IgE levels. The results suggest that, in some patients, mast cell mediators other than histamine play a significant part in immediate-type allergic reactions of skin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.1996.d01-744.x
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  • 5
    Electronic Resource
    Electronic Resource
    Mast cells are one major source of interleukin-4 in atopic dermatitis (1994)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 131 (1994), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Several reports have shown the presence of T-helper lymphocytes with Th2 characteristics in the skin lesions of atopic dermatitis (AD). However. Th2 cells themselves require an exogenous pulse of IL-4 to initiate their differentiation and synthesis of IL-4. As mast cells have recently been shown to contain IL-4, this finding prompted us to investigate IL-4 in mast cells of AD lesions, to determine if they might provide the IL-4 pulse needed by the Th2 cells.In this study, we measured IL-4 immunoreactivity in mast cells of non-lesional and lesional skin sections from 20 patients with AD. Ten patients with nummular eczema (NE) without any atopic features or background, and five healthy subjects, served as the control groups. Mast cells were first identified using an enzyme-histochemical staining method for tryptase. Subsequently, the sections were photographed, the tryptase stain was removed, and IL-4 was demonstrated with a polyclonal antibody. The sections were photographed again, and the percentage of IL-4-positive mast cells was calculated.The percentage of mast cells exhibiting IL-4 immunoreactivity in the upper dermis in lesional vs, non-lesional skin was 66±18% vs. 37±18% in AD (P〈0.0001, paired t-test), but only 46±19% vs. 31±22% in NE. In the skin of healthy controls, only 23±25% of the mast cells were positive for IL-4. In addition, a significant difference was found between lesional skin of AD vs. NE patients (P〈0.008, unpaired t-test). Moreover, the staining intensity of IL-4 in mast cells was clearly increased in the lesional compared with the non-lesional AD skin. Mast cells appeared to be the main cell type containing IL-4 in 40% of the lesional AD skin specimens, whereas in the remaining 60% prominent IL-4-positive mononuclear cell infiltrates were also present. In the non-lesional skin, mast cells appeared to be the main cell type containing IL-4 in all specimens. These results indicate that mast cells are one major source of IL-4 in lesional and non-lesional AD skin, and they could contribute significantly to the development of AD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1994.tb08522.x
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  • 6
    Electronic Resource
    Electronic Resource
    Interleukin-4-positive mast cells are highly associated with the extent of immediate allergic wheal reaction in the skin (2001)
    Copenhagen : Munksgaard International Publishers
    Allergy 56 (2001), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: In addition to histamine, mast cells contain other potent mediators which can contribute to the allergic wheal reaction in the skin. Methods: To study the association of tryptase-, chymase-, and interleukin-4 (IL-4)-positive mast cells with the size of the prick-test wheal reaction, 50 sensitive atopic subjects were prick-tested with the cow-dander allergen on the forearm skin, and the wheal area was measured. A corresponding site of intact healthy-looking skin was biopsied and examined enzyme-histochemically for tryptase and chymase. A double-staining method was used to demonstrate the immunoreactivity of IL-4 and chymase inhibitors (α1-proteinase inhibitor and α1-antichymotrypsin) in mast cells. The levels of total and cow-specific immunoglobulin E (IgE) were measured in serum. Results: The number of tryptase- and chymase-positive mast cells or those containing chymase inhibitors revealed no correlation with the wheal reaction. In contrast, both the percentage and the number of IL-4-positive mast cells showed significant positive correlation with the wheal size per se (P〈0.0001), as well as with the ratio of the wheal size by cow allergen to that by histamine control (P〈0.003). In addition, tryptase-, chymase-, and IL-4-positive mast cells correlated with total IgE, but not with specific IgE, levels, and they showed no relation to the clinical manifestation of atopic disease, asthma or atopic dermatitis. Conclusions: The novel finding was that IL-4-positive, but not tryptase- and chymase-positive, mast cells are intimately associated with the extent of the prick-test wheal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1398-9995.2001.00833.x
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  • 7
    Electronic Resource
    Electronic Resource
    Changing trends in the incidence of non-Hodgkin's lymphoma in Europe (1997)
    Springer
    Annals of oncology 8 (1997), S. 49-54 
    Details
    ISSN: 1569-8041
    Keywords: changing incidence ; epidemiology ; NHL ; population-based registries ; REAL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Non-Hodgkin's lymphoma (NHL) is not a uniform disease entity, and inorder to investigate the reported changes in incidence we have set up astudy in seven population-based cancer registries in Europe. The study isdesigned to look at changes in the incidence of total NHL and diseasesubgroups using standard definitions and methodology. The registries arebased in Leeds, Dijon, Kuopio, Odense, Florence, Eindhoven, and Ragussa. Theclassification system we have used is based on the REAL classification andhas utility for epidemiological studies. We have used it to convert datasets which have utilized both local cases and the ICD-O classification. Inorder to improve data reproducibility, CLL/LL, myeloma/MGUS, lymphoblasticdisease, and Hodgkin's disease have been excluded because of the difficultyin defining incident cases accurately. The preliminary results of this studyshow that there is still an upward trend in incidence rate and that inYorkshire this is 3% per annum in total NHL. The subgroups which areincreasing are extranodal and nodal peripheral T-cell lymphoma. Similarincreases in incidence have been reported for the other registries. Weconclude that there is a continued upward trend in incidence of NHL, thecauses of which are uncertain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008269930158
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  • 8
    Electronic Resource
    Electronic Resource
    Enzyme- and immunohistochemical localization of mast cell tryptase in psoriatic skin (1989)
    Springer
    Archives of dermatological research 281 (1989), S. 387-391 
    Details
    ISSN: 1432-069X
    Keywords: Psoriasis ; Epidermis ; Mast cells ; Tryptase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The localization of mast cell tryptase in involved and noninvolved skin sections from 12 psoriatic patients was investigated using both enzyme- and immunohistochemical staining techniques. Each involved skin section contained an increased number of tryptase-positive mast cells in the superficial dermis as compared with corresponding noninvolved skin sections. The substrate-hydrolyzing and inhibition properties for tryptase activity in involved and noninvolved psoriatic skin sections were identical with each other as well as with those previously described in normal human skin or mastocytoma skin sections. In four patients, epidermal enzyme activity was observed, but only in the involved skin. None of the uninvolved sections showed tryptase activity in the epidermis. This activity was not inhibited by α-antitrypsin, and after removing the enzyme-histochemical stain with Tween 20, positive results obtained with tryptase-specific antibody were found in the same locations. In addition, tryptase-positive cells were detected in close contact to lesional epidermis, but without epidermal staining in four patients. In the epidermis, the positive staining was granular, and active tryptase was detected as far as the stratum corneum. This study is the first description of the presence of active mast cell tryptase in psoriatic epidermis, where this enzyme may have a role in increased cell division.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00455322
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  • 9
    Electronic Resource
    Electronic Resource
    Quantitative analysis of contact sites between mast cells and sensory nerves in cutaneous psoriasis and lichen planus based on a histochemical double staining technique (1991)
    Springer
    Archives of dermatological research 283 (1991), S. 433-437 
    Details
    ISSN: 1432-069X
    Keywords: Sensory nerves ; Mast cells ; Psoriasis ; Lichen planus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the present study was to test further our previous hypothesis that the inflammatory reaction in psoriasis is neurogenic. For this purpose, contact sites between mast cells and sensory nerves were morphometrically analysed in the basement membrane zone, papillary dermis and three dermal zones of lesional/non-lesional psoriatic and lichen planus skin as well as in healthy control skin. The analyses were made on sections stained with a histochemical double stain developed for this study. With the double stain, active mast cell tryptase was stained blue enzyme histochemically, and the sensory nerves black using specific monoclonal anti-neurofilament antibodies with immunogold. In psoriatic lesions, both mast cells and mast cell — nerve contacts were markedly more frequent in the basement membrane zone and in the papillary dermis when compared with the corresponding areas in the other groups. Mast cell numbers were increased in both lesional and symptom-free skin in lichen planus, but no increase was found in the mast cell — nerve contacts. Increased contacts between mast cells and sensory nerves indicate that the elements exist for neurogenic inflammation in psoriatic lesions. These increased contacts are not due to the extensive inflammatory reaction only, because they were not observed in lichen planus lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00371778
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  • 10
    Electronic Resource
    Electronic Resource
    Mast cell tryptase and chymase in developing and mature psoriatic lesions (1993)
    Springer
    Archives of dermatological research 285 (1993), S. 184-192 
    Details
    ISSN: 1432-069X
    Keywords: Mast cells ; Proteases ; Psoriasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The number and distribution of mast cells in nonlesional and lesional skin samples from 13 psoriatic patients were analyzed enzyme- and immunohistochemically. Mast cell tryptase was stained with the sensitive substrate Z-Gly-Pro-Arg-4-methoxy-2-naphthylamide, and chymase with Suc-Val-Pro-Phe-MNA and monoclonal B7 anti-chymase antibody. In addition, healthy-looking skin from 27 psoriatic patients was tape-stripped resulting in induction of the Köbner response in 9 patients. Sequential biopsies were taken before and after (7, 14 and 21 days) tape-stripping, and both tryptase and chymase were stained enzyme-histochemically. In nonlesional psoriatic skin, 70 ± 24% (mean ± SD) of the mast cells contained chymase enzyme activity, and 78 ± 18% chymase immunoreactivity. About 10% of the chymase-immunoreactive cells lacked chymase activity. In lesional psoriatic skin, tryptase-positive cells were increased in number throughout the dermis but especially beneath the epidermis. Chymase immunoreactivity paralleled the tryptase activity, whereas chymase activity was strongly diminished both in terms of mast cell numbers and in staining intensity in the papillary dermis. The apparent inactivation of chymase may be due to the action of the chymase inhibitors, α1-antitrypsin and α1-antichymotrypsin, localized immunohistochemically in mast cells of lesional and nonlesional psoriatic skin. In the developing psoriatic lesion, mast cells displaying chymase activity were already 27–38% decreased in number in the upper dermis on day 7 after tape-stripping, along with the first clinical signs of psoriasis. Earliest alterations in tryptase-positive cells were observed on day 14 as increased mast cell contacts with the epidermis combined with only a slight increase in mast cell numbers in the upper dermis. During the development of a psoriatic lesion, TC mast cells (tryptase+, chymase+) increase in number in the upper dermis, but chymase becomes inactive at an early stage. The abundant presence of active trypase but inactive chymase in the upper dermis may have a potential role in psoriasis since both of these enzymes can process several biologically active peptides and proteins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00372007
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