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Biomedical subjects

A Scheynius

Publications and source records attributed to A Scheynius.

At least 55 records · Page 3Linked to original sources
PubMed1999

Sensitization to allergens of house-dust mite in adults with atopic dermatitis in a cold temperature region.

BACKGROUND: An IgE-mediated contact reaction to airborne allergens has been suggested as one important pathogenetic mechanism in atopic dermatitis (AD). The house-dust mite (HDM) might be a common allergen involved. In Scandinavia, sensitization to HDM has been rare, probably because of the cold, dry climate. However, recent studies indicate high levels of domestic mites and HDM allergen in 15-20% of homes in central and northern Sweden. METHODS: To evaluate the importance of the HDM in patients with AD in the Stockholm region, we screened 81 adult Stockholm residents with AD, for the prevalence and degree of sensitization to the HDM, according to specific IgE (RAST), skin prick test (SPT), and atopy patch test (APT). We also assessed the HDM exposure in their homes and correlated the results with clinical history, severity of the dermatitis, and type of residence during childhood and today. RESULTS: The sensitization rate to HDM was high (56% according to RAST, 24% according to SPT, and 47% according to APT), and 20% of the patients were exposed to HDM allergens in their beds. Mite exposure seemed to aggravate the dermatitis in highly sensitized patients. CONCLUSIONS: The results indicate that we have to take the HDM into account when discussing aggravating factors in adult patients with AD in the Stockholm region.

Adolescent↗
PubMed1999

Increased occurrence of IgE+ and FcepsilonRI+ cells in adenoids from atopic children.

BACKGROUND: To examine the influence of atopy on the different cell populations in adenoids, we investigated the presence of IgE+ cells, cells expressing the high-affinity receptor for IgE (Fc(epsilon)RI), and various other cell populations in adenoid tissue, in atopic and nonatopic children with otitis media with effusion (OME) or adenoid hyperplasia (AH). METHODS: Cryostat sections of adenoids from 14 atopic and 16 nonatopic children suffering from long-lasting OME (n=15) or obstructive AH (n=15) were investigated with immunohistochemical markers for T-cell subsets, mast cells, eosinophils, plasma cells, CD25, CD1a, IgE, and Fc(epsilon)RI. RESULTS: Sensitization to allergens was correlated to an increase of IgE+ cells in the epithelium (P<0.01), the extrafollicular area (P<0.0001), and the follicles (P<0.001) of the adenoids and an increase of Fc(epsilon)RI+ cells in the extrafollicular area (P<0.01). A minority of the IgE+ cells were plasma cells. No significant differences in cells stained for IgE, Fc(epsilon)RI, or the other markers were observed between patients with OME and AH. CONCLUSIONS: Atopy is associated with increased numbers of IgE+ and Fc(epsilon)RI+ cells in adenoids irrespective of whether the child has OME or AH.

Adenoids↗
PubMed1999

Direct Ni2+ antigen formation on cultured human dendritic cells.

The possible direct antigen formation of Ni2+ on antigen-presenting cells (APCs) was studied with cultured human dendritic cells (DCs) obtained from 10 subjects contact allergic to Ni2+ and six non-allergic control individuals. All contact allergic subjects showed a significantly increased peripheral blood mononuclear cell (PBMC) response in vitro to Ni2+. DCs were expanded from the plastic-adherent cell fraction of PBMCs by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days to obtain immature DCs, and with the addition of monocyte-conditioned medium for another 4 days, for DC maturation. The DCs were pulsed for 20 min with Ni2+ (50 micrometers) in protein-free Hank's balanced salt solution (HBSS) and added to freshly prepared autologous responder PBMCs. With five allergic subjects, immature DCs pulsed with Ni2+ demonstrated a significant capacity to activate Ni2+-reactive lymphocytes. With the remaining five patients and the six controls no difference in lymphocyte proliferation was observed between Ni2+-pulsed and non-pulsed immature DCs. In contrast, with mature Ni2+-pulsed DCs from both 'positive responder' (n=4) and 'non-responder' (n=4) patients, there was a significantly stimulated PBMC proliferation, whereas with the controls (n=4) still no activation was observed. Our results indicate that direct formation of the antigenic determinant of Ni2+ on APCs is possible and that Ni2+ uptake and processing mechanisms may not play a major role. Differences in the ease of activation of Ni2+-reactive lymphocytes are discussed in terms of a possible heterogeneity in the availability of Ni2+-reactive groups presented on endogenous peptides bound in the antigen binding groove of human leucocyte antigen (HLA) class-II molecules.

Adult↗
PubMed1999

Peripheral blood T-cell receptor beta-chain V-repertoire in atopic dermatitis patients after in vitro exposure to Pityrosporum orbiculare extract.

The yeast Pityrosporum orbiculare belongs to the normal cutaneous flora but is also considered to be one of the factors that may contribute to atopic dermatitis (AD). In the present study we investigated the possibility that P. orbiculare can act with superantigen activity in AD. P. orbiculare-reactive T-cell lines (TCLs) were obtained after stimulation of peripheral blood mononuclear cells (PBMC) with P. orbiculare extract. T-cell receptor beta-chain V-segment (TCRBV) usage was investigated using monoclonal antibodies and flow cytometry. We could not find any difference in TCRBV usage between AD patients (n = 10) and healthy controls (n = 5), either in fresh PBMC or in P. orbiculare-reactive TCLs. Compared with their original PBMCs the P. orbiculare-reactive TCLs showed a decreased usage of several TCRBVs, although increased usage of certain TCRBVs could be seen in some of the individuals. Further analysis of the CDR3-length polymorphism exhibited a shift in CDR3-length distribution, indicating oligoclonal expansion of T cells specific to different antigens in the P. orbiculare extract. In conclusion we have not found any evidence for superantigen activity in P. orbiculare extract, but our data support the importance of classical major histocompatibility complex (MHC)-restricted allergens in P. orbiculare.

Adolescent↗
PubMed1999

Localization of interleukin-13 gene-expressing cells in tuberculin reactions and lesional skin from patients with atopic dermatitis.

Interleukin (IL)-13 is a cytokine thought to play an important role in IgE-mediated allergic reactions. The aims of the present study were to localize IL-13 mRNA in positive tuberculin reactions and atopic dermatitis lesions using in situ hybridization and to study the possible influence of atopy on the cytokine gene expression in tuberculin reactions. Punch biopsy specimens were taken from tuberculin reactions in 17 nonatopic and 12 atopic (Phadiatop positive), but otherwise healthy, individuals 72h after injection of purified protein derivative, from chronic lichenified lesions and nonlesional skin in six patients with atopic dermatitis and from normal skin in 12 healthy individuals. IL-13-mRNA-producing cells were located mainly in the dermal-cell infiltrates, both in atopic dermatitis lesions and tuberculin reactions. In the atopic dermatitis lesions, IL-13-mRNA expression was found in close apposition to the epidermis. Higher numbers of IL-13-mRNA-producing cells were observed in the dermal-cell infiltrates of chronic lichenified skin lesions of patients with atopic dermatitis (13.3 cells/mm2, range 0.6-42.4 cells/mm2) than in the tuberculin reactions (1.1 cells/mm2, range 0-3.8 cells/mm2) (P<0.01) despite the larger cell infiltrates in the tuberculin reactions. No significant difference in IL-13 or interferon-gamma gene expression in the tuberculin reactions was seen between atopic and nonatopic individuals.

Adolescent↗
PubMed1999

Selective cloning of allergens from the skin colonizing yeast Malassezia furfur by phage surface display technology.

The yeast Malassezia furfur, also known as Pityrosporum orbiculare (ovale), is part of the normal microflora of the human skin but has also been associated with different skin diseases including atopic dermatitis. More than 50% of atopic dermatitis patients have positive skin test and specific IgE to M. furfur extracts; however, the pathophysiologic role of these IgE-mediated reactions in the development of the disease remains unknown. The yeast is able to produce a wide panel of IgE-binding proteins, variably recognized by sera of individual patients. In order to assess the contribution of individual components to the disease, highly pure allergen preparations are required. We have cloned M. furfur allergens from a cDNA library displayed on the phage surface, sequenced the inserts and produced recombinant proteins in Escherichia coli. Phage displaying IgE-binding proteins were selectively enriched from the library using IgE from a M. furfur-sensitized atopic dermatitis patient as a ligand. We were able to identify five different inserts coding for IgE-binding polypeptides. Three of the sequenced cDNA encode incomplete gene products with molecular masses of 21.3 kDa (MF 7), 14.4 kDa (MF 8), and 9.7 kDa (MF 9), respectively, having no sequence similarity to known proteins. The other two cDNA encode allergens of 18.2 kDa (Mal f 5) and 17.2 kDa (Mal f 6). Mal f 5 shows significant homology to M. furfur allergens Mal f 2, Mal f 3 and an Aspergillus fumigatus allergen Asp f 3. Mal f 6 has significant homology with cyclophilin. All of the recombinant polypeptides were capable of binding serum IgE from atopic dermatitis patients in immunoblotting experiments. The availability of pure recombinant M. furfur allergens will allow the careful investigation of the role of IgE-binding proteins in atopic dermatitis.

Allergens↗
PubMed1999

N,N'-Diacetyl-L-cystine-the disulfide dimer of N-acetylcysteine-is a potent modulator of contact sensitivity/delayed type hypersensitivity reactions in rodents.

Oral N-acetyl-L-cysteine (NAC) is used clinically for treatment of chronic obstructive pulmonary disease. NAC is easily oxidized to its disulfide. We show here that N,N'-diacetyl-L-cystine (DiNAC) is a potent modulator of contact sensitivity (CS)/delayed type hypersensitivity (DTH) reactions in rodents. Oral treatment of BALB/c mice with 0.003 to 30 micromol/kg DiNAC leads to enhancement of a CS reaction to oxazolone; DiNAC is 100 to 1000 times more potent than NAC in this respect, indicating that it does not act as a prodrug of NAC. Structure-activity studies suggest that a stereochemically-defined disulfide element is needed for activity. The DiNAC-induced enhancement of the CS reaction is counteracted by simultaneous NAC-treatment; in contrast, the CS reaction is even more enhanced in animals treated with DiNAC together with the glutathione-depleting agent buthionine sulfoximine. These data suggest that DiNAC acts via redox processes. Immunohistochemically, ear specimens from oxazolone-sensitized and -challenged BALB/c mice treated with DiNAC display increased numbers of CD8(+) cells. DiNAC treatment augments the CS reaction also when fluorescein isothiocyanate is used as a sensitizer in BALB/c mice; this is a purported TH2 type of response. However, when dinitrofluorobenzene is used as a sensitizer, inducing a purported TH1 type of response, DiNAC treatment reduces the reaction. Treatment with DiNAC also reduces a DTH footpad-swelling reaction to methylated BSA. Collectively, these data indicate that DiNAC in vivo acts as a potent and effective immunomodulator that can either enhance or reduce the CS or DTH response depending on the experimental conditions.

Acetylcysteine↗
PubMed1998

Role of interferon-gamma in the pathogenesis of LCMV-induced meningitis: unimpaired leucocyte recruitment, but deficient macrophage activation in interferon-gamma knock-out mice.

Generally, interferon-gamma (IFN-gamma) is considered a critical regulator of T cell mediated inflammation. For this reason, we investigated the pathogenesis of lymphocytic choriomeningitis in mice with a targeted defect of the gene encoding this cytokine. Our results revealed that IFN-gamma is redundant in the afferent phase of the antiviral T cell response as well as a local mediator of this T cell mediated inflammatory disease. However, IFN-gamma may play an indirect role as it is involved in reducing extraneural infection that may compete with CNS for available effector cells. Analysis of the inflammatory exudate disclosed that leucocyte recruitment was unimpaired in the absence of IFN-gamma as was the upregulation of ICAM-1 and VCAM-1 on endothelium at the inflammatory site. However, local macrophage activation (production of tumor necrosis-alpha and NO) was significantly impaired. Notably, a viral peptide could also elicit a T cell mediated inflammatory response in virus-primed IFN-gamma knock-out mice, indicating that redundancy of this cytokine as a proinflammatory mediator is not restricted to inflammatory reactions triggered by an active infection. Thus, T cell mediated inflammation may be induced in the absence of IFN-gamma and local macrophage activation.

Animals↗
PubMed1998

Reconstructed human epidermis composed of keratinocytes, melanocytes and Langerhans cells.

In addition to their basic biological interest, models of reconstructed epidermis provide useful tools for in vitro assessment of the toxicology and efficacy of new chemicals and drugs. The fact that the majority of these in vitro models are composed only of keratinocytes has excluded their use in the fields of skin pigmentation and immunology. After the successful introduction of functional melanocytes into the epidermal reconstruct, the integration of Langerhans cells remains an important challenge, particularly since after isolation of Langerhans cells from human epidermis, these cells cannot be subcultured and do not integrate into the reconstructing epidermis. The authors show that cord blood derived and CD34+ progenitors isolated from the peripheral blood give rise to residential Langerhans cells when co-seeded with normal human keratinocytes.

Cell Culture Techniques↗
PubMed1998

HLA-DM is expressed on the cell surface and colocalizes with HLA-DR and invariant chain in human Langerhans cells.

The subcellular distribution patterns of molecules involved in the process of antigen loading [HLA-DR, HLA-DM, and the cytoplasmic and luminal parts of the invariant chain (Ii, CD74)] were investigated in Langerhans cells (LC), both qualitatively and quantitatively. The analysis was performed by immunofluorescence labelling of acetone-fixed vertical cryostat sections from normal human skin specimens and subsequent examination using confocal laser scanning microscopy (CSLM). The intensity-modulated multiple-wavelength scanning (IMS) technique was used to enhance channel separation when scanning dual-labelled specimens. The mean (n = 9) relative epidermal volumes of reactivity were: HLA-DR 8%+/-3%, HLA-DM 6%+/-2%, luminal Ii 6%+/-2%, and cytoplasmic Ii 4%+/-1%. The difference between HLA-DR and the other epitopes was significant at the P<0.001 level. All molecule combinations, except the combination of HLA-DM and luminal Ii (which was not studied), were to various extents colocalized. Experiments performed on unfixed epidermal sheets showed that HLA-DM is present on the cell surface of LC, suggesting that HLA-DM may interact with HLA-DR on the surface to induce peptide loading.

Adult↗
PubMed1998

Free radicals as potential mediators of metal-allergy: Ni2+- and Co2+-mediated free radical generation.

The generation of free radicals by Ni(2+) and Co(2+) was studied at physiological pH in H(2)O(2)-containing solutions in the absence and presence of various radical-mediating ligands and in human peripheral blood mononuclear cell (PBMC) cultures. With ESR spectroscopy, free radical species were identified and quantitated by spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Co(2+) generated hydroxyl radicals from H(2)O(2) in PBS solutions containing glutathione (GSH) or histidine (His). Omission of GSH or His from the reaction mixture significantly reduced the ESR-signal, indicating the importance of metal-chelation in free radical generation. Carnosine did not significantly enhance the reactivity of Co(2+) toward H(2)O(2), whereas cysteine (Cys) and N-acetylcysteine (NAC) suppressed free radical generation. Under identical reaction conditions, Ni(2+) was markedly less reactive toward H(2)O(2) in comparison with Co(2+). GSH, His, Cys and NAC did not enhance free radical generation of Ni(2+) from H(2)O(2). However, in the presence of carnosine weak but significantly enhanced ESR intensities were found. Incubation of PBMC cultures from healthy subjects with Co(2+) (10-50 microM) yielded the DMPO-.OH adduct, suggesting Co(2+)-mediated hydroxyl radical generation. In contrast, incubation of PBMC cultures with Ni(2+) (10-50 microM) did not produce a detectable ESR-signal. Ascorbic acid efficiently inhibited Co(2+)-mediated free radical generation in PBS solutions and PBMC cultures. The observed difference in free radical generating capacity between Ni(2+) and Co(2+) is of interest with respect to the absence of cross-reactivity between the two metal-ions in experimental allergic contact dermatitis.

Acetylcysteine↗
PubMed1998

Culture of human epidermal Langerhans cells in a skin equivalent.

Langerhans cells (LCs) have been cultured in a skin equivalent (SE). Seventy-two SEs were produced by inserting skin biopsies from nine subjects into dermal equivalents consisting of fibroblasts in a collagen matrix. The SEs were cultured in a serum-free medium containing 2-mercaptoethanol with or without 5 ng/mL granulocyte-monocyte colony-stimulating factor (GM-CSF). The SEs were cultured for 12 or 15 days. In the latter case, 0, 1 or 10 microg/mL cyclosporin A (CyA) was added for the last 3 days. The SEs were then snap frozen for immunohistochemistry. The migration of LCs was evaluated by measuring the distances from the inserted skin biopsy in the SEs to the HLA-DR + and CD1a+ dendritic cells localized at the longest distance from the biopsy in the epidermal outgrowth on both sides of the biopsy. The density of these cells was estimated in 15-day-old SEs by counting them on both sides of the inserted skin biopsy and dividing the number of positive cells by the migrated distances. All epidermal outgrowths (range 0.6-3.7 mm) were well differentiated and displayed HLA-DR+, CD1a+ and Lag+ dendritic cells. Only occasionally were CD83+ cells observed. In the 15-day-old SEs cultured with GM-CSF, a few CD86+ cells were seen in the epidermal outgrowths and occasionally CD80+ cells. The median (n = 4) density of CD1a+ and HLA-DR+ cells in the epidermal outgrowths at day 15 was 5.2 and 9.1 cells/mm, respectively. GM-CSF did not influence migration in 12-day-old SEs, but there was a tendency to increased migration of HLA-DR+ dendritic cells in 15-day-old SEs. CyA did not affect migration or density. We conclude that LCs can be cultured with an in vivo-like density in a SE. They express the phenotype of immature antigen-presenting cells efficient in capturing and processing antigen. This model may be suitable for studies of the initial phase of contact allergic reactions.

Cells, Cultured↗
PubMed1998

Pityrosporum orbiculare-reactive T-cell lines in atopic dermatitis patients and healthy individuals.

The yeast Pityrosporum orbiculare is one of the factors that may contribute to atopic dermatitis (AD). In the present study we compared the T-cell response to P. orbiculare in 12 AD patients with specific immunoglobulin (Ig)E antibodies (Ab) in serum against P. orbiculare with that of six non-atopic healthy controls. Freshly isolated peripheral blood mononuclear cells (PBMC) were cultured for 3 days in the presence of P. orbiculare extract. The proliferative response as measured by [3H]-thymidine incorporation was significantly higher in the AD patients than in the healthy controls (P < 0.05). Furthermore, significantly higher levels of interleukin (IL)-5 (P < 0.05), as analyzed by ELISA, were produced by PBMC from the AD patients compared to the healthy controls. Pityrosporum orbiculare-reactive T-cell lines (TCL) established by P. orbiculare stimulation of PBMC for 11 days produced significantly higher levels of IL-4 and IL-5 after stimulation with anti-CD3 Ab and showed a higher IL-4/interferon (IFN)-gamma ratio (P < 0.05) in the AD patients compared to the healthy controls. The higher proliferative PBMC response to P. orbiculare and the Th2-like cytokine production by P. orbiculare-stimulated TCL from AD patients indicate that P. orbiculare may play a role in maintaining skin inflammation in AD.

Adolescent↗
PubMed1998

Free radicals as potential mediators of metal allergy: effect of ascorbic acid on lymphocyte proliferation and IFN-gamma production in contact allergy to Ni2+ and Co2+.

A possible free radical mechanism in metal allergy was investigated in peripheral blood mononuclear cell (PBMC) cultures from 6 subjects, contact allergic to Ni2+ and Co2+, and 6 control individuals. Ni2+ and Co(2+)-mediated free radical generation was studied with electron spin resonance spectroscopy. The immune response was characterized by cellular [methyl-3H]thymidine uptake and interferon-gamma (IFN-gamma) production Ni2+ and Co2+ (10-50 microM) significantly increased lymphocyte proliferation and IFN-gamma production in PBMC cultures from contact allergic subjects in comparison with cultures from controls. Inhibition of Co(2+)-mediated free radical generation by ascorbic acid did not influence cellular [methyl-3H]thymidine uptake and IFN production. Detectable amounts of free radicals were not obtained with Ni2+. We therefore conclude that it is unlikely that free radicals are involved in contact allergy to Ni2+ and Co2+.

Adult↗
PubMed1998

Differential epidermal expression of the invariant chain in allergic and irritant contact dermatitis.

Allergic contact dermatitis and irritant contact dermatitis have different pathogenic mechanisms. It is therefore plausible that the epidermal expression of HLA-DR and the invariant chain associated with antigen processing and presentation might differ between allergic contact dermatitis and irritant contact dermatitis. We have quantified the volume of epidermal HLA-DR and invariant chain reactivity and the total epidermal volume in allergic contact dermatitis and irritant contact dermatitis using confocal laser scanning microscopy and indirect immunofluorescence on acetone-fixed 25 microns thick vertical skin sections. Eight nickel allergic patients were patch-tested with 5% nickel sulfate and 8 healthy volunteers were patch-tested with 4% sodium lauryl sulfate. Skin biopsy specimens were taken at 0, 6, 24, and 72 h after application of the patch tests. Sodium lauryl sulfate induced a statistically significant increased epidermal volume at 24 h and 72 h compared to 0 h and 6 h (p < 0.003 and p < 0.001, respectively), whereas an increase in epidermal volume in the allergic contact dermatitis group was not noted until 72 h after patch testing with nickel sulfate compared to 0, 6 h (p < 0.001) and 24 h (p < 0.004). No significant changes in the epidermal volume of HLA-DR reactivity were found at any time point within or between the two groups, nor was there any significant change in the epidermal volume of invariant chain reactivity in the allergic contact dermatitis group. In the irritant contact dermatitis group, however, the epidermal volume of invariant chain reactivity was significantly reduced from 17 +/- 8 x 10(3) microns 3 at 24 h to 9 +/- 3 x 10(3) microns 3 at 72 h (p < 0.04), which was also significantly lower than the 14 +/- 4 x 10(3) microns 3 observed in allergic contact dermatitis at 72 h (p < 0.01). Furthermore, the invariant chain expression was significantly lower than the HLA-DR reactivity in the irritant contact dermatitis group at 72 h (p < 0.001). The decrease of invariant chain reactivity at 72 h in irritant contact dermatitis might reflect an epitope-induced alteration by sodium lauryl sulfate or a down-regulated biosynthesis of the invariant chain due to variance in local cytokine production between allergic contact dermatitis and irritant contact dermatitis.

Adult↗
PubMed1998

Late skin-prick-test reactions to malted wheat. Clinical observations and immunohistochemical characterization.

This study reports late skin-prick-test (SPT) reactions in seven bakers and seven control subjects to malted wheat appearing after 6-10 h, and not preceded by an immediate-phase reaction. Two subjects in each group had a history of atopic symptoms and were Phadiatope positive. Serologic IgE analysis (RAST) of normal wheat flour and of malted wheat grain was negative in all subjects. Skin biopsy specimens were obtained 16-18 h after SPT to malted wheat grain and to histamine and from untested skin. The late SPT reactions in all participants had an urticarial appearance, clinically and in routine histology. Immunohistologically mild to moderate perivascular dermal cell infiltrates were observed in both groups, consisting mainly of CD4+ and HLA-DR+ cells. The number of CD1a+ epidermal cells was statistically significantly higher (P < 0.01) in the bakers' prick-tested skin compared to that of the controls, a fact which might reflect preparedness to react upon challenge. There were no statistical differences between the two groups in IgE+ epidermal cells or epidermal cells expressing the high-affinity IgE receptor (Fc epsilon RI). However, there was a correlation between serum-IgE levels and the number of IgE+ epidermal cells. The late skin reactions observed in both bakers and controls were probably more of an irritant or toxic than immune-mediated nature, but they raise the question of whether skin contact with malted flour contributes to an unfavorable prognosis of hand eczema in bakers.

Adult↗
PubMed1998

Lack of antagonism to Ni2+ and Co2+ contact allergy from other essential divalent metal ions.

The potential antagonistic effects of Ca2+, Cu2+, Fe2+, Mg2+, Mn2+ and Zn2+ on contact allergy to Co2+ and Ni2+ were studied. The immune response was characterized by the Co2+ or Ni2+ mediated cellular [methyl-3H]thymidine uptake in peripheral blood mononuclear cell (PBMC) cultures from 6 subjects contact-allergic to Co2+ and Ni2+ and 6 non-allergic control individuals. Results from the in vitro experiments were further evaluated with Co2+-sensitized guinea pigs according to the modified Freund's complete adjuvant test. Ni2+ and Co2+ (10-50 microM) significantly increased the lymphocyte proliferation in PBMC cultures from contact-allergic subjects in comparison with those from control individuals. Pretreatment of the PBMCs with Ca2+, Fe2+, Mg2+ (10-100 microM) or Mn2+ (1-10 microM) did not influence, while Zn2+ (100 microM) enhanced, and Cu2+ (5 and 10 microM) markedly reduced the Ni2+ and Co2+ mediated cellular [methyl-3H]thymidine uptake. The inhibition of the Ni2+- and Co2+-induced cell proliferation by Cu2+ in vitro was probably related to toxicity, since the viability of the cells was significantly reduced by applied combinations of Ni2+ or Co2+ with Cu2+. Topical pretreatment of Co2+-sensitized guinea pigs with maximum non-irritating doses of CuCl2 x 2H2O (0.8%) did not affect the challenge testing to CoCl2 x 6H2O (0.1 and 0.3%). In conclusion, our combined in vitro and in vivo results indicate that Ca2+, Cu2+, Fe2+, Mg2+, Mn2+ and Zn2+ are not able to antagonise the formation of Ni2+ and Co2+ antigens.

Adult↗