Airborne contact dermatitis from colophony: phototoxic reaction?
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Air Pollutants, Occupational↗
Biomedical subjects
A Kapp
Publications and source records attributed to A Kapp.
Altered production of immuno-modulating cytokines in patients with atopic dermatitis.
Atopic dermatitis (AD) represents an inflammatory skin disorder which is characterized by many signs of immunodeficiency. Particularly, decreased lymphoproliferative responses upon stimulation with mitogens as well as bacterial antigens were reported repeatedly. Since there is increasing evidence for a network of immuno-modulating cytokines playing a crucial role in the regulation of immunity and inflammation, in the present study we investigated whether an altered production of these mediators is one of the pathomechanisms responsible for the altered immune response in AD. For this purpose the 24-h supernatants of LPS- and PHA-stimulated or unstimulated mononuclear cells (MNC) from patients with AD of a moderate to severe disease activity and from nonatopic healthy controls were tested for Interleukin-1 (IL-1) and Interleukin-2 (IL-2) activity. Whereas supernatants of unstimulated MNC of AD patients and controls did not contain significantly different levels of these cytokines, LPS-stimulated MNC of AD patients released significantly less IL-1 in the supernatants. Similarly, the production of IL-2 by PHA-stimulated MNC of AD patients was significantly decreased in comparison to the controls. Moreover, there was a strong correlation between IL-1 and IL-2 levels. These findings indicate that diminished lymphoproliferative responses in AD may partly be caused by a decreased capacity of MNC to release immuno-modulating cytokines, even upon appropriate stimulation.
Dermatitis, Atopic↗
[Specific IgE to Staphylococcus aureus in patients with atopic dermatitis].
It is a well-known feature of atopic dermatitis (AD) that the patient's skin is heavily colonized by Staphylococcus aureus. S. aureus-derived antigens may be important triggers of the immune response and may significantly contribute to the genesis of the cutaneous pathology of AD. Therefore, serum samples of 52 patients with AD, all of whom had signs of moderate to severe disease activity, were tested for antistaphylococcal IgE antibodies with RAST discs coupled to antigens derived from Wood 46 strain. Total IgE concentrations and specific IgE to nine different common allergens were also determined. Only 2 patients showed significant levels of specific IgE antibodies to S. aureus (RAST class greater than or equal to 2). Both these patients were found to have high total IgE and significant levels of specific IgE to all nine common allergens tested. One of the patients had marked eosinophilia. We conclude that the presence of specific IgE to S. aureus is not correlated with the disease activity in AD. Specific antistaphylococcal IgE does not represent an important diagnostic feature in AD, but may be of importance for the detection of subgroups within patients affected by AD.
Adult↗
Granulocyte-activating mediators (GRAM): III. Further functional characterization of monocyte-derived GRAM.
As shown previously monocytes upon stimulation with bacterial lipopolysaccharides (LPS) release granulocyte-activating mediator(s) (M-GRAM) which induced a long-lasting chemiluminescence (CL) response in human granulocytes. M-GRAM could be separated from interleukin-1 alpha and beta, interleukin-2, interferon alpha and gamma, granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF), since these cytokines are shown to be unable to induce a significant CL response. In contrast, granulocyte macrophage colony stimulating factor (GM-CSF) and particularly tumor necrosis factor (TNF) are important triggers of the oxidative burst and they are capable of inducing a CL response. TNF activity but not lymphotoxin (LT) activity could be demonstrated in M-GRAM samples. A polyclonal rabbit IgG as well as a monoclonal antibody to recombinant human TNF which neutralized the TNF activity in M-GRAM preparations did not substantially block the CL signal. Furthermore, M-GRAM-induced CL response was not significantly inhibited by a polyclonal calf antiserum to human recombinant GM-CSF. For further functional characterization of M-GRAM-induced granulocyte activation different assays were performed in order to compare GM-CSF and TNF: (a) SOD-inhibitable cytochrome C-reduction (.O2-); (b) horseradish peroxidase-mediated oxidation of phenol red (H2O2); (c) the release of peroxidase; (d) ultrastructural detection of hydrogen peroxide production; and (e) scanning and transmission electron microscopy (SEM and TEM). Significant release of .O2- was induced by M-GRAM, TNF, and GM-CSF, whereas H2O2 production was significantly stimulated only by M-GRAM and TNF, as shown by functional and ultrastructural assays.(ABSTRACT TRUNCATED AT 250 WORDS)
Biological Factors↗
Decreased production of interferon in whole blood cultures derived from patients with psoriasis.
Patients suffering from psoriasis show many alterations with respect to their immune system as documented by in vitro test systems. In the present study we investigated the in vitro production of interferons (IFN) of leukocytes from psoriatic patients to stimulation with a variety of IFN inducers. Furthermore, the lymphoproliferative responses were tested. Whole blood cultures of 30 psoriatic patients showing moderate to severe disease activity and 21 cultures from healthy controls were stimulated with the mitogens PHA, ConA, and PWM, with PPD and Tetanus Antigen as IFN gamma inducers and with C. parvum, PolyI-PolyC, and Herpes simplex virus as inducers of IFN alpha. Interferon activity was tested in the supernatant of 48-h cultures by using an antiviral assay. Lymphoproliferation was assayed in 5-d cultures in parallel. Psoriatic patients showed a significantly decreased IFN production to all the stimuli tested. There were no significant differences in the lymphoproliferative responses; only the response to PWM was slightly decreased. The decreased IFN production by leukocytes from psoriatic patients seems to be very remarkable since increased susceptibility to infections is not generally known in these patients.
Cells, Cultured↗
Human granulocyte-macrophage colony stimulating factor: an effective direct activator of human polymorphonuclear neutrophilic granulocytes.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) was shown to modulate different granulocyte functions. In the present study we investigated the effect of purified and recombinant human GM-CSF, particularly on the oxidative metabolism of isolated human granulocytes. In addition, ultrastructural changes upon stimulation were evaluated. For detection of granulocyte activation the following assay systems were used: 1) lucigenin-dependent chemiluminescence (CL), 2) superoxide-dismutase (SOD) inhibitable cytochrome C-reduction (superoxide), 3) horseradish peroxidase-mediated oxidation of phenol red (hydrogen peroxide), 4) release of myeloperoxidase, 5) ultrastructural detection of hydrogen peroxide-production, and 6) scanning and transmission electron microscopy (SEM and TEM, respectively). A significant CL response was seen upon stimulation with recombinant human GM-CSF at concentrations ranging from 1 to 10(3) U/ml. The CL response started within 5-10 min with a maximum at 60-90 min and lasted more than 3 h. Thereafter granulocytes were completely deactivated to restimulation with the same mediator and with Tumor Necrosis Factor, but responded to other triggers of the oxidative burst, whereas the response to f-met-leu-phe was significantly increased. The CL signal was completely blocked by an antiserum to GM-CSF. Moreover, the response was significantly inhibited by SOD and D-Mannitol, suggesting the involvement of distinct reactive oxygen species (ROS) in generating the CL response. Significant amounts of superoxide were detected within 180 min after stimulation with GM-CSF, whereas release of hydrogen peroxide and peroxidase were only minimal as shown by functional and ultrastructural assays. Activation of granulocytes could be visualized by SEM and TEM. GM-CSF stimulated cells showed an increased adherence to the substratum developing polarized filopodia and an increased number of intracellular vesicles within 30 min after addition of the stimulus. The results clearly demonstrate that GM-CSF directly stimulates granulocytes and, particularly, their oxidative metabolism. Therefore, GM-CSF which is probably released by epidermal cells appears to be a candidate for neutrophil activation in the skin, and thereby may play a crucial role in inflammatory skin diseases.
Chemotaxis↗
Elevated levels of interleukin 2 receptor in sera of patients with atopic dermatitis and psoriasis.
Elevated levels of serum interleukin 2 receptor (IL2R) represent an early measure of T cell activation. The concentration of IL2R was measured in the sera of patients with atopic dermatitis (n = 58) or psoriasis, without psoriatic arthritis, (n = 26), who had moderate to severe disease activity, and in non-atopic healthy controls (n = 37) by an ELISA technique. Serum IL2R levels were found to be significantly elevated in both disease groups compared with the controls. The increase in serum IL2R may be due to T cell activation in the dermis.
Adolescent↗
Modulation of human neutrophilic granulocyte functions by recombinant human tumor necrosis factor and recombinant human lymphotoxin. Promotion of adherence, inhibition of chemotactic migration and superoxide anion release from adherent cells.
Recombinant human tumor necrosis factor (TNF) and recombinant human lymphotoxin (LT) were analyzed for their effects on inflammation-related functions of human polymorphonuclear neutrophilic granulocytes (PMN) in vitro, TNF at a concentration of 10 U/ml (corresponding to 10(-11) mol/l) enhanced PMN adherence to nylon fibres. It strongly inhibited the chemotactic migration of PMN in the Boyden chamber assay towards the chemotactic tripeptide formyl-methionyl-leucyl-phenylalanine (FMLP), C5a, LTB4 and a monocyte-derived chemotaxin (MOC) without affecting random migration and without being chemotactic itself. It did not stimulate superoxide anion (-O2.) production of PMN in suspension. However, it induced considerable -O2. release from PMN that had become adherent on nylon fibres. All these effects were abrogated by prior incubation of the cytokine with polyclonal and monoclonal antibodies against TNF. LT concentrations of 1,000 U/ml or higher were required to observe a moderate inhibition of chemotactic migration towards the above chemotactic factors and to elicit some -O2. production from nylon fibre-adherent PMN. LT did not increase the adherence of PMN to nylon fibres and it was not chemotactic. The results indicate that TNF is a potent modulator of PMN functions.
Cell Adhesion↗
[Pathogenesis of atopic dermatitis].
Atopic dermatitis (AD) is a familial inflammatory skin disorder, which is characterized by extreme pruritus, the typical morphology and distribution, the chronic or chronically relapsing course, and the personal or family case history of atopy (asthma, allergic rhinitis, atopic dermatitis); moreover, we find a variety of additional features, which are either less specific or relatively rare. Although this disease has been well-known since the beginning of the century, we have not clearly understood its pathogenesis so far. This article reviews the reported deviations of the immune system and the alterations of the mediators of inflammation as well as the abnormalities of cyclic nucleotide regulation. These findings are correlated to the clinical symptoms. The following topics have been dealt with in detail: association with HLA-antigens, elevation of serum IgE and generation of IgE immune complexes, numerical and functional deficiencies of T-suppressor cells, involvement of granulocytes, alterations of mediators of inflammation, and particularly, observations on the cAMP-phosphodiesterase. These extremely complex findings, which are based on the interaction between disregulation of the autonomous nervous system and alterations of the immune system, may provide a better understanding of the pathogenesis of atopic dermatitis.
Cyclic AMP↗
Granulocyte-activating mediators (GRAM). II. Generation by human epidermal cells--relation to GM-CSF.
In the present study we investigated the capability of human epidermal cells to generate granulocyte-activating mediators (GRAM). It could be shown that human epidermal cells as well as an epidermoid carcinoma cell line (A431) produce an epidermal cell-derived granulocyte-activating mediator (EC-GRAM) which stimulates human granulocytes to release significant levels of toxic oxygen radicals as measured by a lucigenin-dependent chemiluminescence (CL). For further characterization of EC-GRAM the A431 cell line was used. Supernatants of A431 cells usually contained maximal EC-GRAM levels within 24 h of incubation. Factor production was enhanced by bacterial lipopolysaccharide (LPS), but not by silica particles and PHA. Moreover, freeze-thaw lysates of A431 cells and extracts of heat-separated human epidermis contained significant levels of EC-GRAM. Preincubation of granulocytes with EC-GRAM resulted in an enhanced response to subsequent stimulation with the chemotactic peptide f-met-phe. In contrast EC-GRAM did not affect the response to PMA or zymosan particles. However, EC-GRAM treated granulocytes were unresponsive to restimulation with EC-GRAM. Upon high performance liquid chromatography (HPLC) gel filtration EC-GRAM eluted within two major peaks exhibiting a molecular weight of 17 kD and 44 kD.(ABSTRACT TRUNCATED AT 250 WORDS)
Biological Products↗
Production of interferon and lymphoproliferative response in whole blood cultures derived from patients with atopic dermatitis.
Enhanced susceptibility to viral infections has been reported repeatedly in atopic dermatitis (AD). A difference in the capacity to produce interferons (IFN) in response to viral antigens may be the cause. In the present study we investigated the in vitro IFN production of leukocytes from AD patients in response to different stimuli. Furthermore, the lymphoproliferative responses were tested. The patients showed moderate to severe disease activity. Whole blood cultures of 25 AD patients and 21 healthy nonatopic controls were stimulated with the mitogens phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM), with tuberculin derivative (PPD) and tetanus antigen as IFN-gamma inducers, and with C. parvum, poly I-poly C, and herpes simplex virus (HSV) as inducers of IFN-a. Lymphoproliferation was assayed in 5-day cultures in parallel. In AD no significant difference of the IFN production was found in comparison with the controls with any stimuli tested. The lymphoproliferative response of leukocytes of patients with AD was significantly decreased upon stimulation with PHA, Con A, PWM, and PPD. We suggest that in AD the described susceptibility to viral infections is not due to an altered capability of leukocytes to generate IFN.
Antigens↗
Induction of human granulocyte chemiluminescence by bacterial lipopolysaccharides.
Bacterial lipopolysaccharides (LPS) have been reported to influence the oxidative response of human polymorphonuclear leukocytes (PMN). However, results sometimes conflict. In the present study, we demonstrated that activation of human PMN by LPS depends on the class (smooth [S] or rough [R]) to which the LPS belongs. Lucigenin-dependent chemiluminescence was used to assay oxygen radical production. Twenty different S- and R-form LPS and free lipid A were tested in concentrations of 0.01 to 100 micrograms/ml. S-form LPS activated PMN only at maximal concentrations and to a low extent. R-form LPS and free lipid A were potent inducers of granulocyte chemiluminescence even at a concentration of 0.1 microgram/ml. The results indicated that R-form LPS are very effective in inducing granulocyte chemiluminescence, whereas true S-form preparations are inactive. It is not known at present whether this higher activity is due to a more lipophilic character of R-form LPS or whether the presence of the O polysaccharide in S-form LPS exerts an inhibitory effect on their action on granulocytes.
Humans↗
Chemiluminescence response of polymorphonuclear leukocytes in atopic dermatitis.
Atopic dermatitis (AD) is characterized by many signs of immunodeficiency. Our interest was to investigate if there are also alterations of the chemiluminescence (CL) response of polymorphonuclear leukocytes (PMN) as a measure of the release of toxic oxygen radicals. Isolated PMN of 13 patients with AD with mild to moderate disease activity were stimulated with a chemotactic peptide (f-met-phe), zymosan-activated serum (ZAS), zymosan particles and phorbolmyristate acetate. In the AD group, we found a significantly decreased response after stimulation with ZAS in comparison to the controls. With the other stimuli tested no significant difference was detected. The decreased response of PMN to stimulation with ZAS from patients with AD associated with a normal reactivity to the other stimuli could be due to specific desensitization of the PMN by C5a in vivo.
Adult↗
Chemiluminescence response of human B-cell lines.
Epstein-Barr virus (EBV)-transformed human B lymphoblastoid cells share certain properties with monocytes: they are capable of presenting protein antigens to antigen-specific T-lymphocytes and of releasing an Interleukin 1-like factor. It was our interest to study whether transformed B-cells resemble monocytes by generating toxic oxygen radicals. Human B-cell lines were developed from human peripheral blood lymphocytes by EBV-transformation. The induction of the respiratory burst in the B-cells was assessed by chemiluminescence (CL) in the presence of lucigenin. B-cells were stimulated with phorbol-myristate-acetate (PMA), zymosan particles, the chemotactic peptide f-met-phe, the complement split product C5a and with a recently described granulocyte activating cytokine (GRAM). Stimulation with PMA elicited a distinct CL-response in the tested B-cell lines. The CL-signal was significantly reduced by superoxide dismutase, but not by D-mannitol and catalase. No significant response to any of the other stimuli was detected. Furthermore, none of the stimuli induced a luminol-enhanced CL signal, which, in contrast to lucigenin, is dependent on the presence of peroxidase. Our results indicate that EBV infected B-cells were able to generate significant amounts of reactive oxygen species, particularly superoxide. It appears that virus transformation uncovers genetic information which is usually not expressed in non-transformed B-cells.
B-Lymphocytes↗
A novel interleukin stimulating free radical production by granulocytes.
Polymorphonuclear granulocytes (PMN) are potent producers of free oxygen-derived radicals. Since other granulocyte functions are affected by interleukins, we investigated whether free-radical production can be initiated by a similar mediator. For estimation of free radical production, SOD-inhibitable lucigenin-dependent chemiluminescence and SOD-inhibitable cytochrome C reduction were used. As a source of interleukins, serum-free 24 h culture supernatants of human mononuclear cells (MNC) stimulated with bacterial lipopolysaccharide were prepared. Addition of such supernatants to PMN caused stimulation of sod-inhibitable chemiluminescence and superoxide production. Studies with separated MNC showed that monocytes were the cellular source of the activity. Biochemically, this activity of the supernatants was due to a heat-labile glycoprotein with a MW of approx. 60 KDa. This mediator, termed granulocyte chemiluminescence inducer (GCI), appears to be distinct from interleukin 1 (alpha and beta) and interferon (alpha and gamma). In conclusion we describe a novel monokine, granulocyte chemiluminescence inducer (GCI), which initiates granulocyte free radical production. This interaction of monocytes and granulocytes may also in vivo constitute a new and potent pathway leading to stimulation of free oxygen production by granulocytes.
Antibodies, Monoclonal↗
[Modulation of the oxidative metabolism of granulocytes by nonsteroidal anti-inflammatory agents].
In the present study we investigated the influence of the following four nonsteroidal anti-inflammatory drugs on the oxidative response of isolated human granulocytes: carprofen, tenoxicam, indomethacin, piroxicam. The effect of these drugs was assessed by a lucigenin-dependent chemiluminescence. In the experiments carprofen significantly stimulated granulocytes. Indomethacin exhibited a similar effect. However, there was no strong dose-response relation. Preincubation of granulocytes with the four tested drugs resulted only at the highest concentrations in a reduced response of the cells to stimulation with the chemotactic peptide f-met-phe and zymosan-particles. The response of the cells stimulated with zymosan-activated serum as a source of the complement split product C5a and to stimulation with the tumor-promotor phorbol-myristate-acetate was not significantly altered. Only carprofen showed a dose-response-related inhibitory effect. In conclusion, the four tested nonsteroidal anti-inflammatory drugs demonstrate different effects on the oxidative metabolism of human granulocytes. Lucigenin-dependent chemiluminescence, hereby, could be a sensitive tool for measuring the effect of pharmaca on granulocyte function in vitro.
Anti-Inflammatory Agents, Non-Steroidal↗
Modulation of granulocyte oxidative response by recombinant interferon alpha 2 and gamma.
Interferon (IFN) has been described to influence various cellular functions. In this study we investigated whether the oxidative response of polymorphonuclear leukocytes (PMN) is also affected by IFN. In order to exclude the possible influence of impurities in IFN preparations, only recombinant human IFN alpha 2 or gamma were used. Lucigenin-dependent chemiluminescence (CL) of PMN was measured to assess the production of oxygen radicals. IFN gamma at a concentration of more than 10 ng/ml elicited a minimal CL response in PMN. When PMN were incubated with IFN gamma for 1 h and then stimulated with chemotactic peptide f-met-phe (FMP), zymosan-activated serum (ZAS), zymosan particles, or phorbol-myristate acetate (PMA), the CL response was increased as consequence of the generally enhanced oxidative metabolism. IFN alpha 2 showed no such effect at any concentration tested. A 5-min pretreatment with IFN gamma decreased the ZAS response but did not affect the reaction to the other stimuli. The possibility of a generation of IFN by PMN during the assay could be excluded as no IFN activity could be detected in an antiviral assay after stimulation of PMN for 6 h with PolyI X PolyC, LPS, ConA, C. parvum, PMA, zymosan, or FMP. The modulation of granulocyte activity by IFN gamma may be important in the regulation of the anti-inflammatory response of PMN.
Acridines↗
Inhibitory effect of sulfonated shale oils (ammonium bituminosulfonate) on the stimulation of neutrophilic granulocytes by the chemotactic tripeptide f-Met-Leu-Phe.
Sulfonated shale oils (ammonium bituminosulfonate, ichthammol, Ichthyol), shown previously to induce the directed migration of human neutrophils in Boyden chambers and to inhibit the directed migration towards the chemotactic factors C5a, LTB4, and f-Met-Leu-Phe, were studied for their effect on other neutrophil functions, which are stimulated by chemotactic factors. Like other chemotactic factors ammonium bituminosulfonate increased the adherence of neutrophils to nylon fibers, but it did not induce the release of the primary granule enzyme glucosaminidase from cytochalasin B-treated cells and it did not stimulate the production of oxygen radicals as measured by lucigenin-dependent chemiluminescence if studied under nontoxic conditions. When added together with the chemotactic tripeptide f-Met-Leu-Phe, ammonium bituminosulfonate inhibited adherence augmentation, enzyme release, and oxygen-radical production induced by the chemotactic factor. The results indicate that ammonium bituminosulfonate not only inhibited chemotactic migration but the whole spectrum of neutrophil functions induced by a chemotactic factor.
Cell Adhesion↗