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1.
Summary Numbers and volume fractions of mast cells in nonlesional and chronic lesional skin of psoriatic patients were compared with those of normal control skin. Mast cell densities were similar in psoriatic nonlesional and normal control skin. The superficial dermis of lesional psoriatic skin contained more mast cells than either normal or nonlesional psoriatic skin. Neither PUVA nor corticosteroid treatment for 3–4 weeks significantly reduced mast cell numbers or volume fractions in lesional skin, although both treatments clinically and histologically markedly improved the lesions. The results indicate that the initiation of the healing process in psoriatic plaques is not correlated with the mast cell density. The remaining high mast cell density may be normalized later, or after a longer therapy. 相似文献
2.
Mast cell survival and apoptosis in organ-cultured human skin 总被引:2,自引:0,他引:2
Mast cells accumulate and persist predominantly in the upper dermis of the skin but the mechanism for this is obscure. The skin is normally exposed to external air, which is essential for the maturation of the epidermis and probably also the dermis. In order to clarify the importance of air exposure on dermal mast cells, skin organ culture at the air-liquid interface (ALI) and submerged (SM) in medium (10% fetal calf serum and Dulbecco's modification of Eagle's medium) was used to study changes in tryptase-, chymase- and Kit-positive mast cell numbers during cultivation for up to 14 days. In addition, possible apoptosis (TACS TdT in situ apoptosis detection method) in chymase-positive mast cells was studied during the culture. In the less-physiologic SM culture, the number of Kit-positive mast cells decreased rapidly on day 1-2 and tryptase-positive cells decreased markedly on day 14. This decrease in mast cell numbers can be explained by the finding that a rapid increase in the apoptosis index of mast cells was induced on day 1-2. In contrast, in the more physiologic ALI culture, the number of Kit-positive cells was sustained over 1-2 days but then decreased on day 7. In addition, tryptase-positive cells decreased steadily in number but not to the same extent as those in the SM culture. Moreover, the increase in the apoptosis index of mast cells was delayed until day 7 in the ALI culture. Addition of exogenous stem cell factor (up to 200 ng/ml) to the SM culture could not prevent the decay in tryptase- and chymase-positive cells. However, stem cell factor reduced significantly the number of Kit-positive cells already on day 2 indicating that the cells had responded. Addition of histamine (0.25 or 1 mM) or tumor necrosis factor-alpha (500 or 2000 U/ml) caused a decrease in the number of tryptase- and Kit-positive cells in the SM culture. In conclusion, a novel finding was that air exposure in the ALI culture markedly delayed the rapid apoptosis and subsequent decrease in mast cell numbers noted to occur in the SM culture. Stem cell factor could not prevent the rapid decrease in mast cell numbers. Histamine and tumor necrosis factor-alpha are possible factors promoting the decline in mast cells. 相似文献
3.
I. T. Harvima A. Naukkarinen K. Paukkonen R. J. Harvima M. -L. Aalto L. B. Schwartz M. Horsmanheimo 《Archives of dermatological research》1993,285(4):184-192
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, 1-antitrypsin and 1-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. 相似文献
4.
T. E. Damsgaard Anne Braae Olesen Flemming Brandt Sørensen Kristian Thestrup-Pedersen Peter Oluf Schiøtz 《Archives of dermatological research》1997,289(5):256-260
Stereological quantification of mast cell numbers was applied to sections of punch biopsies from lesional and nonlesional
skin of atopic dermatitis patients and skin of healthy volunteers. We also investigated whether the method of staining and/or
the fixative influenced the results of the determination of the mast cell profile numbers. The punch biopsies were taken from
the same four locations in both atopic dermatitis patients and normal individuals. The locations were the scalp, neck and
flexure of the elbow (lesional skin), and nates (nonlesional skin). Clinical scoring was carried out at the site of each biopsy.
After fixation and plastic embedding, the biopsies were cut into 2 μm serial sections. Ten sections, 30 μm apart, from each
biopsy were examined and stained alternately with either toluidine blue or Giemsa stain and mast cell profile numbers were
determined. The study yielded the following results: (1) in atopic dermatitis lesional skin an increased number of mast cell
profiles was found as compared with nonlesional skin, (2) comparing atopic dermatitis skin with normal skin, a significantly
increased number of mast cell profiles per millimetre squared was found in specimens from the neck, (3) staining with toluidine
blue yielded a lower number of mast cell profiles than Giemsa staining, (4) the use of Carnoy’s fixative resulted in a lower
mast cell profile count than the use of formaldehyde, and (5) there was no statistically significant correlation between the
clinical score and the number of mast cell profiles per millimetre squared. Using stereological techniques, this study indicated
that mast cells might participate in the inflammatory process in skin leading to atopic dermatitis.
Received: 17 April 1996 相似文献
5.
Mast cells are known to be the effector cells of immediate-type allergy, but experimental evidence obtained during the last decade has revealed their role in innate and acquired immunity. Upon activation mast cells can undergo an anaphylactic or piecemeal degranulation or degranulation-independent mediator secretion, resulting in rapid or slow release of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express different receptors and ligands on the cell surface, molecules that can activate the cells of the immune system, such as different subsets of T cells. All these mediators and cell surface molecules can promote inflammation in the skin. During the last years, a new role for mast cells has emerged; induction of tolerance or immunosuppression and interaction with regulatory T cells. However, the mechanisms that switch the proinflammatory function of mast cells to an immunosuppressive one are unknown. In this review, the immunoregulatory function of mast cells and its relation to skin inflammation are discussed. 相似文献
6.
T. Demitsu Tomoharu Kiyosawa Maki Kakurai Satoru Murata Hideo Yaoita 《Archives of dermatological research》1999,291(6):318-324
Abstract We studied the effects of stem cell factor (SCF) on human skin mast cell (HSMC) survival and the proliferation of neurofibroma
(NF) cells in transplanted NF in nude mice. Small pieces of cutaneous NF from a patient with von Recklinghausen’s disease
were transplanted subcutaneously into nude mice. Recombinant human SCF (10 or 100 ng) was injected six or seven times around
the NF transplantation sites over 11 days (i.e. every other day). The number of HSMCs was reduced in vehicle-injected NF compared
to the amount present before transplantation. In contrast, NF-transplanted animals that were injected with SCF (10 or 100
ng) showed preservation of mast cell numbers in the tissue. Using computerized image analysis, mast cell size in SCF-treated
NF transplants was significantly altered (larger at the 10 ng dose, and smaller at the 100 ng dose) compared with the size
before transplantation or in vehicle-injected tissue. Furthermore, at the higher SCF dose (100 ng) PCNA-positive NF cells
showed a significant increase. These results indicate that HSMCs in transplanted NF tissue retain their capacity to respond
to SCF in vivo, and that SCF contributes to the regulation of both HSMC survival and size in cutaneous NF. In addition, activated
HSMCs induced by SCF may be involved in the growth of cutaneous NF in von Recklinghausen’s disease. Thus, this experimental
model may be useful in the study of the cellular interactions between HSMCs and other stromal cells in cutaneous NF.
Received: 9 June 1998 / Received after revision: 30 November 1998 / Accepted: 11 December 1998 相似文献
7.
Abstract The release of cytokines from cutaneous cells may be of major importance in the initiation and development of many inflammatory
skin disorders. For example, tumor necrosis factor-alpha (TNF-α), which in healthy skin is found preformed only in mast cells,
is able to induce the expression of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1). Increased
expression of ICAM-1 occurs in keratinocytes in lesional skin of psoriasis and atopic dermatitis (AD) and it is considered
to be an important initiator of leucocyte/keratinocyte interactions in skin inflammation. We counted the mast cells showing
TNF-α immunoreactivity using a double-staining method in nonlesional and lesional skin sections from 12 patients with AD and
12 patients with psoriasis. The percentage of TNF-α+ mast cells in lesional and nonlesional AD skin was 36 ± 22% and 21 ± 15% (P < 0.018, paired t-test), respectively, and in psoriatic skin was 16 ± 25% and 15 ± 15%, respectively (P < 0.89, paired t-test). We also cultured whole skin biopsies taken from the healthy-looking skin of psoriatic and AD patients in the presence
of mast cell degranulator compound 48/80, which resulted in focal expression of ICAM-1 in the epidermis. In cultured keratinocytes,
both histamine and an extract of a human mast-cell line (HMC-1) induced ICAM-1 immunostaining only in occasional cells, but
the combination of histamine and the HMC-1 extract resulted in intense ICAM-1 staining in numerous cells. This enhancement
of ICAM-1 staining was abolished by preincubation of the HMC-1 extract with anti-TNF-α antibody. These results suggest that
the degranulation of mast cells induces the expression of ICAM-1 in keratinocytes probably via TNF-α and histamine.
Received: 8 August 1997 相似文献
8.
Andreas D. Katsambas Anthony J. Karpouzis Elma Koumantaki-Mathioudaki Joseph L. Jorizzo 《Journal of the European Academy of Dermatology and Venereology》1999,13(3):155-165
AIM: To review our present knowledge about mastocyte origin, mastocytosis classification and management. METHODS: Literature review. RESULTS: Mastocytoses are chronic and recurrent disorders with symptoms which might either be limited only to the skin or to internal organs as well. The mastocytes, coming from bone marrow progenitor cells, migrate to tissues where they participate in inflammation and in cellular immunity as well as in the metabolism of connective and osseous tissues. Their proliferation causes the appearance of mastocytoses. The classification of the clinical manifestations of the mastocytoses into cutaneous, reactive (under the influence of the degranulator factors) and systemic disease, facilitates dialog among clinicians. Determination of prognosis and appropriate therapeutic regimens depend on individual features. CONCLUSIONS: Mastocytosis diagnosis is verified by histological study of skin lesion biopsy material. Management is symptomatic and unfortunately does not eradicate the disease. 相似文献
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10.
Badertscher K Brönnimann M Karlen S Braathen LR Yawalkar N 《Archives of dermatological research》2005,296(10):503-506
Mast cell chymase is a chymotrypsin-like serine proteinase primarily stored in secretory mast cell granules. Mast cell chymase has various effects on angiotensin, metalloproteases, lipoproteins, procollagen, neuropeptides and cytokines. Recent studies have demonstrated that chymase inhibitors inhibit skin inflammation. In this study we sought to determine the role of mast cell chymase in atopic dermatitis (AD) in comparison with its role in psoriasis and normal skin. Skin biopsy specimens were obtained from non-lesional and lesional skin of patients with chronic AD and psoriasis and from normal skin of non-atopic and non-psoriatic controls. The number of mast cells containing chymase was determined by immunohistochemistry using a chymase-specific monoclonal antibody. A significantly (P<0.05) enhanced number of chymase-positive cells was found in lesional AD skin as compared to normal skin as well as to lesional and non-lesional skin of patients with psoriasis. A significant (P<0.05) increase in the number of chymase-positive cells was also found in non-lesional AD skin in comparison to psoriasis. An enhanced, albeit not statistically significant difference was noted in non-lesional AD skin as compared to normal skin. In conclusion, these results suggest that mast cell chymase may play an integral part in eliciting and maintaining cutaneous inflammation in AD but not in psoriasis. The increased proteinase activity of mast cell chymase may also be involved in promoting a skin barrier defect in AD, which subsequently enhances the skins permeability to allergens and microbes and thereby aggravates the eczema. 相似文献
11.
Cathleen A. Suender Mandy Leist Magnus Åbrink Patricia Valentin Astrid Geldmacher Martin Steinhoff Martin Metz Marcus Maurer 《Experimental dermatology》2018,27(1):50-57
Thrombin, a key player in coagulation, is widely held to induce and promote inflammation. As of now, the features, kinetics and control of thrombin's proinflammatory effects on the skin remain to be characterized in detail. We, therefore, injected thrombin into the ear skin of mice and observed strong, dose‐dependent and transient ear swelling responses as well as mast cell (MC) degranulation. Unexpectedly, thrombin induced even stronger, not reduced, ear swelling in MC‐deficient KitW‐sh/W‐sh mice. Prior local reconstitution of KitW‐sh/W‐sh mice with MCs inhibited this effect, indicating that MCs may contribute to the control of thrombin‐induced skin inflammation. In line with previous studies, we found that MCs express the thrombin receptors PAR1, PAR3 and PAR4, thrombin induces direct and dose‐dependent MC degranulation, and that degranulated MCs inactivate thrombin. Further findings suggested that MC‐mediated protection from thrombin‐induced inflammation is likely to rely on the effects of MC proteases. We show for the first time that MC‐deficient mice and MC protease 4‐deficient mice with normal numbers of MCs show markedly increased ear swelling in response to thrombin as compared to wild‐type mice. Taken together, these results suggest that thrombin‐induced skin inflammation is controlled, in part, by MC protease 4 released from activated MCs. For MC‐driven diseases such as chronic spontaneous urticaria, which has been linked to increased thrombin generation, this might mean that MCs may contribute to the resolution of skin inflammatory responses. 相似文献
12.
Mast cells and macrophages in early relapsing psoriasis 总被引:4,自引:0,他引:4
Summary Five patients with widespread plaque-type psoriasis were treated continuously with clobetasol under occlusion. Clinical healing was seen after 6–10 days of treatment. All plaques treated in this way clinically relapsed approximately 12 days later. During the period of remission, sequential biopsies were taken and prepared for light and electron microscopy. Histologically, the earliest indications of relapse were endothelial alterations (swelling, intercellular widening) followed by the appearance of mast cells around the postcapillary venules; these mast cells showed signs of degranulation. Hours later, activated macrophages showing pericellular edema were present, and these migrated into the epidermis soon after. Associated with the presence of macrophages, there was a complete loss of desmosome-tonofilament complexes. Later, lymphocytes and neutrophils were seen. Under these experimental conditions, the psoriatic-tissue alterations appear to have been initiated by degranulating mast cells as well as by macrophages which later invaded the epidermis.This paper was presented at the 14th Meeting of the ESDR (Amsterdam, April 1984) 相似文献
13.
Mast cell accumulation and cytokine expression in the tight skin mouse model of scleroderma 总被引:4,自引:0,他引:4
The tight skin (Tsk) mouse develops many pathological changes seen in human scleroderma, such as increased collagen content and mast cell density. Although associations between mast cell expansion and skin fibrosis have been reported, the mechanisms underlying mast cell accumulation remain unclear. In this study, we have measured the density of skin mast cells in Tsk mice and their normal littermates (pa/pa) of 4-36 weeks of age, and in the skin heterografted between Tsk and pa/pa mice. Cytokines related to mast cell differentiation, proliferation and migration were examined by using RNase protection assays. Skin mast cell density in Tsk mice was significantly increased from 12 weeks of age, compared to that in pa/pa mice. The expression of transforming growth factor-beta1 (TGF-beta1), and to a lesser extent, stem cell factor (SCF) and interleukin-15 (IL-15) mRNA was higher in Tsk mice, compared to that in control mice. Mast cell density was unchanged in Tsk skin grafted onto pa/pa hosts, but dramatically increased in pa/pa skin grafted onto Tsk hosts. This latter mast cell hyperplasia was associated with the increases in mRNA levels of TGF-beta1, SCF and IL-15, whereas little change in cytokine levels was seen in heterografted Tsk skin. These results suggest that locally produced cytokines in Tsk skin influence mast cell accumulation in this animal model of human scleroderma. 相似文献
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15.
Abstract: Mast cells are known to be important effector cells in innate immune responses to bacterial infections. However, up to now, neither the mechanisms nor the relevance of mast cell degranulation in innate skin immune responses to bacteria have been adequately addressed. In this article, we show that the bacterial toxins streptolysin O (SLO) and α-toxin potently induce degranulation of mast cells in vitro and in vivo . Furthermore, intradermal injection of the toxins results in pronounced skin inflammation, which either resolves quickly within a few h (SLO-induced inflammation) or presents a chronic process with ongoing inflammation for weeks (α-toxin). Interestingly, mast cells mediated the inflammatory effects of SLO, but in contrast limited inflammatory skin responses to α-toxin. These findings further support the hypothesis that mast cells are critically involved in initiating and modulating optimal host responses to bacteria by either inflammatory or anti-inflammatory effects, depending on the course of the host reaction induced by the pathogen. 相似文献
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Mast cells (MC) are of hematopoietic origin but complete their differentiation exclusively within tissues. The mediators that positively or negatively affect the maturation process are incompletely defined. Here, the human MC line HMC-1 (subclone 5C6) was used along with several treatments (IL-4, IL-6, NGF), either alone or in combination, and MC differentiation was monitored by flow-cytometric analysis of c-kit, tryptase, and FcRI expression. Of the different treatments, IL-4 displayed the clearest effects by suppressing the expression of the three markers and inhibiting cellular growth, while the other cytokines had no (NGF) or negligible (IL-6) effects only. The downregulating effects of IL-4 could not be overcome by any other treatment. There is some controversy in the literature as to the impact of IL-4 on the MC lineage. To determine whether the effects from IL-4 were differentiation stage dependent, two further human MC subsets (skin MC and LAD 2 cells) were investigated. No effects on c-kit and FcRI expression were noted when terminally differentiated skin MC were used as target cells, while a modest downregulation of c-kit was observed with intermediately matured LAD 2 cells. In sharp contrast to HMC-1 5C6 cells, the survival of skin MC was significantly enhanced by IL-4 treatment. Our data therefore imply that at a lower maturation stage, IL-4 acts as a negative regulator of the MC lineage, but that this property disappears or is even reversed upon terminal differentiation of the cell. Our study provides direct proof that the effects of IL-4 vary substantially in the course of MC maturation. 相似文献
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20.
Mast cell ontogeny and apoptosis 总被引:5,自引:0,他引:5
Abstract The 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 survival in the periphery. 相似文献