Sture Lidén

Glutamate- and aspartate-like immunoreactivities in human normal and inflamed skin

SummaryThe presence of glutamate/aspartate-like immunoreactivity was studied in normal human skin and in skin with gold-induced inflammation. In normal skin all epithelial cells were glutamate and, apparently more weakly, aspartate immunoreactive. Both glutamate and aspartate immunoreactivities were also found in macrophage-like, HLA-DR positive cells in the dermis and in the epidermis. The intensity of glutamate and especially aspartate-like immunoreactivities seemed to be increased in the epidermis and dermis of the inflamed as compared to the normal skin, and this increase was particularly pronounced in the HLA-DR positive (dendritic) cells in the epidermis. Numerous cells, often of the mononuclear type, in the superficial dermis expressed glutamate- and aspartate-like immunoreactivities in the inflamed skin and many of these were HLA-DR positive. The functional role of glutamate and aspartate in normal skin, and the significance of the increase in the levels of these amino acids in several cell populations in the inflammatory skin is not known, but modulatory or protective roles may be considered. High concentrations of these amino acids could also induce cell damage. Moreover, the macrophage-like cells in the human skin may have a role in the processing of glutamate and aspartate on a recycling basis.

Patch test reactions to metal salts in patients with oral mucosal lesions associated with amalgam restorations

Patch testing with various metal salts was performed in patients with oral mucosal lesions associated with amalgam restorations, by using polypropylene‐coated aluminium discs Positive reactions to mercuric chloride were obtained in 5/12 (42%) of these patients, but only in 1/11 patients (9%) with oral mucosal lesions unassociated with amalgam restorations and in 3/36 patients (8%)in control group without mucosal lesions. The difference between the former group and the control patients is statistically significant (p< 0.05) In addition, a positive test reaction to copper sulfate was obtained in 2 patients (16%) with amalgam‐associated mucosal lesions and negative reactions to mercuric chloride. 2 of the 5 positive test reactions to mercuric chloride, in the patients with lichenoid mucosal lesions associated with amalgam, became lichenoid and persisted for at lease 3 weeks. The patients with these reactions were also positive at a concentration of 0.05% mercuric chloride, but were‐negative to metallic mercury, in contrast lo 2 other patients in the same group. This indicates the necessity of including mercuric chloride when patch testing such patients.

Immunohistochemical localization of interleukin-6-like immunoreactivity to peripheral nerve-like structures in normal and inflamed human skin.

Interleukin-6-like (IL-6-like) immunoreactivity was sought in inflamed and normal human skin using the same immunohistochemical technique as for detection of neuropeptides. Such immunoreactivity was found in dermal and in a few intraepidermal nerve-like fibres in biopsy specimens from inflamed skin from patients with positive epicutaneous patchtest reactions to nickel sulphate, and in skin specimens from patients with atopic dermatitis and prurigo nodularis. However, IL-6-like immunoreactivity was also found in nerve-like fibres in specimens from nonlesional skin. In skin from patients with positive epicutaneous patch-test reactions there was a statistically significantly (P<0.01) higher number of IL-6-positive nerve fibres in the epidermis than in normal skin, in contrast to the papillary dermis, in which no difference was found. Moreover, there were clusters of nerve-like fibres with IL-6-like immunoreactivity in the dermis of prurigo nodularis lesions. In these nerve-like fibres, the colocalization of the immunoreactivities for IL-6 and calcitonin gene-related peptide was indicated. Localization of immunoreactivity to nerve-like structures surrounding the eccrine sweat glands indicates that IL-6 is present in autonomic as well as in sensory nerve fibres.

Serotonin in human allergic contact dermatitis. An immunohistochemical and high-performance liquid chromatographic study.

Abstract Allergic contact dermatitis (ACD) is a common clinical condition leading to considerable morbidity. We have recently demonstrated that ketanserin, a serotonin antagonist, significantly inhibits nickel sulphate-induced ACD. Furthermore, serotonin-immunoreactive (IR) cells have previously been demonstrated in normal human cutaneous melanocytes. To further elucidate the role of serotonin in cutaneous contact hypersensitivity, we compared ACD involved skin and uninvolved skin from nickel-allergic patients, and normal skin from healthy volunteers, for the presence of serotonin-like immunoreactive cells using immunohistochemistry. In addition, serotonin concentrations in ACD involved and uninvolved skin were compared by high-performance liquid chromatography (HPLC). In the skin of normal healthy volunteers, the serotonin-IR cells were situated in the basal layer of the epidermis. In uninvolved skin the cells were also situated in the basal layer, but they were more numerous and the immunofluorescence intensity was greater. In involved skin, the IR cells were fewer and they were found higher up in the epidermis. Also, the configuration of these cells was different: they showed enlarged and elongated dendrites as well as dendritic spines. The serotonin antiserum-labelled cells in ACD involved skin were also NKI-beteb positive (the latter is known as a reliable marker of melanocytes). The concentration of serotonin in involved skin was significantly higher than that in uninvolved skin in ACD patients ( P < 0.05). Taken together, our previous and present results indicate that serotonin plays an important role in ACD. The basal epidermal serotonin-IR cells are more dendritic in ACD, and are found more superficial in the epidermis, where they might release their content of serotonin, thereby influencing the inflammatory process.

Interleukin (IL)-1 alpha- and -1 beta-, IL-6-, and tumor necrosis factor-alpha-like immunoreactivities in human common and dysplastic nevocellular nevi and malignant melanoma.

Interleukin-1α and -1β, interleukin-6, and tumor necrosis factor-α may have a protective effect against malignant transformation of melanocytes. By using monoclonal and polyclonal antisera we investigated, in paraformaldehyde-fixed tissue, the cellular distribution of these cytokines in human common and dysplastic nevocellular nevi and in malignant melanoma. Generally, the immunolabeling for all of these cytokines was both cytoplasmic and perinuclear as well as present in the basement membrane, which surrounds the individual cells or cellular nests of some of the nevi. In compound and intradermal nevi the immunolabeling was abundant, although there was a variation in the staining intensity between individual cells and even inside a single nevus cell, ranging from weak to strong. There was a strong labeling of the basement membrane around the cellular nests and around individual cells inside or outside the nests in the papillary and reticular dermis. With regard to the common junctional and dysplastic nevi and malignant melanoma, occasional immunolabeling could be seen in some cells within the cellular nests in the junctional area or papillary dermis, ranging from faint to moderate in intensity, but in this case the basement membrane around individual cells or cellular nests was not stained. The staining of nevocellular nevi and malignant melanoma indicates the possibility of these cytokines being synthesized by the nevi and melanoma cells. The labeling of the basement membrane in compound and intradermal nevi suggests that cytokines produced by nevocellular cells may be stored in the basement membrane, from which they could be released upon environmental or mechanical challenge. This distribution pattern would support the hypothesis that these cytokines may protect the common nevi from malignant transformation.

Proinflammatory cytokines and their corresponding receptor proteins in eccrine sweat glands in normal and cutaneous leishmaniasis human skin. An immunohistochemical study

Abstract Paraformaldehyde‐fixed biopsy specimens of normal and chronic cutaneous leishmaniasis human skin were investigated for the presence and cellular distribution of interleukin‐1α, interleukin‐1β, interleukin‐6 and tumour necrosis factor‐α and the corresponding receptors in eccrine sweat glands, using an indirect immunoperoxidase technique. There was cytoplasmic staining for all 4 cytokines as well as their receptor proteins in the clear cells of the eccrine sweat glands of both normal and inflamed skin specimens. No staining could be seen in the dark cells or the myoepithelial cells, neither in normal nor in inflamed skin. However, a difference between normal and inflamed skin was observed in the ductal syslem. Thus, cell layers of the dermal ducts in leishmaniasis skin were stained for all 4 cytokines, with more intense labelling in the basal cell layer of the coiled ducts, while in the normal skin, an intense staining was more evident in the inner luminal layer, with variable and less intense labelling of the basal layer. The immunolabelling for the cytokine receptors within the dermal ducts exhibited similar staining intensity in both luminal and basal cell layers, except in the case of the IL‐6 receptor, which showed a moderate to intense signal in the basal cell layer but a weak staining of the luminal cell layer. Infiltrating inflammatory cells around the sweat gland apparatus in leishmaniasis skin exhibited immunoreactivilies for all cylokines and their corresponding receptors.

Immunohistochemical localization of IL-1 alpha-, IL-1 beta-, IL-6- and TNF-alpha-like immunoreactivities in human apocrine glands

Immunohistochemical localization of IL-1 alpha- and -1 beta, IL-6-, and tumor necrosis factor-alpha-like immunoreactivities in human apocrine glands.

Contact allergy to sorbic acid and Unguentum Merck

Only a few cases of sorbic acid sensitivity resulting from the use of Unguentum Merck (E. Merck Ltd.) are described in the literature (Saihan & Harman 1978, Brown 1979, Coyle et al. 1981). At the Department of Dermatology, University of Umea, Unguentum Merck has often been prescribed since its introduction in Sweden in 1973. Prescriptions of carbamide (urea) 10% in Unguentum Merck as emollients have also been given as well as the topical steroid Corticoderm Cream (E. Merck Ltd.), which also contains Unguentum Merck. Due to therapy failure or worsening of existing eczema a large number of patients have been patch tested to known contact allergens in topical medicaments and to the actual medicament itself. From 1973 to 1980 we have observed 25 cases of contact allergy to sorbic acid (test concentration 2.5% in 95% ale.) and/or to Unguentum Merck or carbamidc-Unguentum Merck (50% in petrolatum). 21 patients were patch tested to sorbic acid; 19 were positive, 2 were negative. The 2 patients with a negative test reaction to sorbic acid were positive to carbamide-Unguentum Merck, and one of them was also positive to the perfume in Unguentum Merck. The 4 patients not tested to sorbic acid had a positive patch test reaction to Unguentum Merck (2 cases) and to carbamide-Unguentum Merck (2 cases). In 20 of these 25 cases the test reaction had a clinical relevance, i.e. the patients eczema had been aggravated by treatment with Unguentum Merck, carbamide-Unguentum and/or Corticoderm Cream and the dermatitis cleared up when the topical therapy was changed. Thus, it has been demonstrated that Unguentum Merck causes a rather high frequency of contact sensitivity.

DIFFERENTIAL EXPRESSION OF NERVE GROWTH FACTOR IN LEISHMANIA MAJOR MURINE CUTANEOUS LEISHMANIASIS

The cross-talk between the immune and nervous systems is becoming an interesting field of research and there is accumulating evidence supporting this notion. In the present study we investigated the levels of nerve growth factor in a murine model of cutaneous leishmaniasis, using a two-site ELISA. Two strains of inbred mice were used for this purpose, namely BALB/c and C57BL/6, genetically susceptible and resistant, respectively, to infection with Leishmania major. This work demonstrates a difference in expression of nerve growth factor in the skin and secondary lymphoid organ microenvironment, as well as in the serum, between these mouse strains. The high nerve growth factor levels in the microenvironment seem to be important and possibly critical for the outcome of the disease. Compared with controls, the resistant strain, C57BL/6, expressed significantly increased nerve growth factor levels in the skin, secondary lymphoid organs and serum at 1 week post-infection, whereas the susceptible strain, BALB/c, showed no change in the skin and a slight increase in the lymphoid organs and serum at this time-point. These high nerve growth factor levels in the early stage of the disease, whether produced directly by the inflammatory cells or indirectly through its induction by other cytokines or both, might indicate a contribution of this neurotrophic factor to differentiation of naive T lymphocytes into either Th1 or Th2 subsets that fundamentally govern the disease outcome. The expression of significantly elevated nerve growth factor levels in the skin and lymphoid organs of C57BL/6 at the late studied time points might suggest a role for nerve growth factor in the resolution of the disease process, which is usually evident from 6 weeks post-infection in this model. The high nerve growth factor levels expressed in the skin, lymph nodes and serum of BALB/c at late stages of the disease may be explained as an attempt to counteract the progression and dissemination of the disease. This investigation adds further experimental evidence for an anti-inflammatory effect of nerve growth factor, possibly through its action as a link between the nervous and immune systems.

Migration-stimulating effect of psoriatic scales on polymorphonuclear leukocytes

SummarySeveral previous studies have demonstrated a chemotactic factor for white blood cells in extracts from psoriatic scales. In the present work, the question was studied whether chemotaxis is a primary or a secondary event in the development of a psoriatic lesion. The migration-stimulating properties of polymorphonuclear leukocytes of different extracts were determined by means of a modified Boyden technique. Aqueous extracts of psoriatic scales were good stimulators of migration of both autologous and homologous leukocytes. Uninvolved skin adjacent to psoriatic plaques (perilesional skin) has previously been shown to differ from control skin in various respects. Extracts of such perilesional skin of psoriatic patients did not have migration-stimulating properties. This result indicates that chemotaxis is a secondary event in the pathogenesis of psoriasis.ZusammenfassungFrühere Untersuchungen haben gezeigt, daß Extrakte von Psoriasisschuppen leukocytenchemotaktische Wirkung besitzen. In dieser Arbeit wurde die Frage studiert, ob Chemotaxis ein primäres oder ein sekundäres Geschehen in der Entwicklung eines Psoriasisherd ist. Die migrationsstimulierenden Eigenschaften polymorphkerniger Leukocyten sind mittels einer modifizierten Boyden-Technik für verschiedene Extrakte untersucht worden. Wäßrige Extrakte von Psoriasisschuppen waren gute Stimulatoren der Migration von autologen und homologen Leukocyten. Die unbefallene Haut in der Nähe von Psoriasisherden (periläsionale Haut) besitzt viele abnorme Eigenschaften, obgleich sie keine klinisch sichtbaren Veränderungen aufweist. Extrakte von periläsionaler Haut weisen keine migrationsstimulierende Wirkung auf. Diese Resultate sprechen dafür, daß Chemotaxis ein sekundäres Phänomen in der Pathogenese der psoriatischen Hautveränderungen ist.