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Biomedical subjects

C Hauser

Publications and source records attributed to C Hauser.

At least 145 records · Page 8Linked to original sources
PubMed1988

Activation and expansion of hapten- and protein-specific T helper cells from nonsensitized mice.

Hapten- and protein-antigen-specific T helper cells are usually expanded in vitro from lymphocytes obtained from sensitized animals. In this paper we report on the primary activation and proliferation in vitro of T helper cells from nonsensitized animals by using syngeneic cultured epidermal Langerhans cells as a source of potent antigen-presenting cells. The primary in vitro proliferation was blocked with monoclonal antibodies to Ia molecules, to lymphocyte function-associated antigen 1 (LFA-1), and to L3T4. T helper cell populations sensitized in vitro to haptens and protein antigens showed hapten- and antigen-specific proliferation when restimulated in vitro with spleen cells. Besides its experimental usefulness, in vitro generation of syngeneic specific T helper cells may afford possibilities for adoptive immunotherapy.

Animals↗
PubMed1987

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↗
PubMed1987

Systemic administration of etretin increases epidermal interleukin I in the rat.

We have studied the effect of systemic administration of etretin (Ro 10-1670) on the epidermal interleukin I (ILI) pool in the rat. Hairless rats were given varying doses of etretin intraperitoneally for 21 days, or a fixed dose for 2, 8 and 16 days. Abdominal skin was taken and processed for light microscopy, autoradiography (using [3H]-thymidine) and ILI assays. ILI was assayed in supernatants of epidermal extracts by both the lymphocyte activating factor (LAF) assay and the stimulation of prostaglandin E2 (PGE2) release from dermal fibroblasts. A significant increase in both LAF and PGE2 stimulatory activities was found during etretin administration. After 21 days' treatment with varying doses there was a two- to three-fold increase as compared to the controls, with a peak at 2 and 5 mg/kg. At a fixed dose a two-fold increase was found after 2 days and a three- to four-fold increase after 16 days; normal pretreatment values were restored 16 days after cessation of etretin. This is the first demonstration in vivo that a retinoid can modulate ILI content in a tissue. As epidermal ILI has been found to be decreased in psoriasis, its modulation by retinoids might have therapeutic significance.

Acitretin↗
PubMed1986

Interleukin 1 is present in normal human epidermis.

We investigated the presence of interleukin 1 (IL 1)-like molecules in normal unstimulated human epidermal tissue. Epidermis from 21 healthy individuals that was prepared by two different methods showed prostaglandin E2 (PGE2) and collagenase stimulating activity for human dermal fibroblasts. All epidermal extracts tested were positive for thymocyte comitogenic activity (lymphocyte activating factor; LAF). Removal of the horny layer decreased epidermal IL 1-like activity. In contrast to epidermal tissue, freshly isolated peripheral blood mononuclear cells (PBMC) contained no detectable PGE2 stimulatory activity. They could, however, produce PGE2 stimulatory activity after culture and stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A). Little membranous IL 1-like activity could be detected in epidermal extracts when using a method that has previously rendered membranous IL 1 from murine proteose peptone-elicited peritoneal macrophages. Gel filtration chromatography yielded double peaks at m.w. approximately 30,000 and approximately 17,000 for all three activities. High pressure liquid chromatography (HPLC) analysis identified two species with a m.w. of approximately 17,000, and one approximately 30,000 species nondissociable in detergent, all having superposable PGE2 and collagenase stimulatory as well as LAF activity. These results establish the existence of IL 1-like molecules, together with a possible precursor, in normal human epidermis. The release of these preformed epidermal IL 1 stores might be important in vivo.

Chromatography, Gel↗
PubMed1986

Expression of the influenza virus haemagglutinin in insect cells by a baculovirus vector.

The insect baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV) has played a major role in studies on the molecular biology of insect DNA viruses. Recently, this system has been effectively adapted as a highly efficient vector in insect cells for the expression of several mammalian genes. A cDNA sequence of the influenza (fowl plague) virus haemagglutinin gene has been inserted into the BamHI site of the pAc373 polyhedrin vector. Spodoptera frugiperda cells were co-transfected with this construct, pAc-HA651, and authentic AcNPV DNA. Recombinant virus was selected by adsorption of transfected cells to erythrocytes followed by serial plaque passages on S. frugiperda cells. We have determined the site of insertion of the haemagglutinin gene into the AcNPV genome by restriction enzyme cleavage and Southern blot hybridization analyses using haemagglutinin cDNA as a probe. The influenza haemagglutinin gene is located in the polyhedrin gene of AcNPV DNA. Immunofluorescent labelling, immunoprecipitation and immunoblot analyses with specific antisera revealed that S. frugiperda cells produce immune reactive haemagglutinin after infection with the recombinant virus. The haemagglutinin is expressed at the cell surface and has haemolytic capacity that has been activated by post-translational proteolytic cleavage. When chickens were immunized with S. frugiperda cells expressing haemagglutinin, they developed haemagglutinin-inhibiting and neutralizing antibodies and were protected from infection with fowl plague virus. These observations demonstrate that the haemagglutinin is processed in insect cells in a similar fashion as in fowl plaque virus-infected vertebrate cells and that it has full biological activity.

Amino Acid Sequence↗
PubMed1986

Intracellular epidermal interleukin 1-like factors in the human epidermoid carcinoma cell line A431.

Normal human epidermal cells produce, in primary culture, activities which stimulate the release of PGE2 and collagenase by dermal fibroblasts; this factor(s) might play an important role in epidermal-dermal interactions. Since these activities were mainly found in the cell lysates with only little being detected in the conditioned media, we investigated further the problem of cell-associated versus released activity in the model of the human epidermoid carcinoma cell line A431. The activities were consistently found in the cell lysate and in the conditioned media only when the cells were leaky. No membrane-associated activities were identified. Purification of the cytosolic activities were identified. Purification of the cytosolic activities yielded two differently charged species both with a MW of approximately 17K. The copurification of PGE2- and collagenase-stimulating activities with thymocyte comitogenic activity suggests a close physiochemical relation to IL-1. The activities described here might therefore correspond to the intracellular counterpart of epidermal IL-1 formerly described as epidermal cell-derived thymocyte activating factor (ETAF) and identified in the conditioned medium of cultured epidermal cells. These observations are of importance when studying the modulation of these activities.

Carcinoma, Squamous Cell↗
PubMed1986

Increased in vitro cell-mediated immune response to staphylococcal antigens in atopic dermatitis.

Atopic dermatitis patients have both a chronic colonization of their skin with Staphylococcus aureus and a delayed cutaneous hyporesponsiveness to intradermally injected staphylococcal antigens. It has not been established whether the cutaneous anergy merely reflects a specific lymphocyte hyporesponsiveness to staphylococcal antigens. Therefore the lymphocyte proliferative response to staphylococci was assessed in twelve patients with slight to severe atopic dermatitis and in eleven healthy subjects. Compared to the normal subjects, the patients showed significantly higher stimulation indices with S. aureus Wood 46 (p less than 0.05) and purified S. aureus cell walls (p less than 0.05). There was no significant correlation between the lymphocyte stimulation and the clinical severity of the disease. Therefore, chronic colonization of the skin of atopic dermatitis patients by S. aureus does not correlate with a defect in the cellular immune response to the bacteria but may rather stimulate such a response.

Adolescent↗
PubMed1986

cis-Urocanic acid does not inhibit mitogen induced lymphocyte transformation in man.

Urocanic acid (UCA) is a photoreceptor in the epidermis which absorbs UVB. To elucidate the role of UCA as an immunomodulator in the mechanism of immune suppression which occurs after UV irradiation in human, we studied the effect trans-UCA as well as that of its UV induced cis-isomer (cis-UCA) on mitogen induced lymphocyte transformation and on delayed type responses elicited by intradermal testing of a standardized battery of microbial antigens. No inhibitory effect was seen either in vitro or in vivo. Our negative results, both in vivo and in vitro, suggest that if UCA and UCA photoproducts exert an immunomodulatory effect, their effect should be analysed by a more subtle evaluation of the immune system.

Double-Blind Method↗
PubMed1986

Normal epidermis contains high amounts of natural tissue IL 1 biochemical analysis by HPLC identifies a MW approximately 17 Kd form with a P1 5.7 and a MW approximately 30 Kd form.

Recently, we demonstrated that normal human epidermis contains IL1. The present work analyses further the significance of this observation by comparing the quantities of epidermal IL1 to those of 7 internal organs in normal rat. Epidermal PGE2 stimulating activity was 200 to 900 fold higher than in the internal organs. Similar results were obtained for the collagenase stimulatory activity and the comitogenic effect on thymocytes. Epidermal IL1 activity in membrane preparations was more than 100 times lower than the activity of the cytosol containing supernatant from the epidermal homogenate. Biochemical analysis by HPLC identified a MW approximately 17 Kd form with a pI 5.7 and a MW approximately 30 Kd form. These results 1) confirm the presence of high amounts of preformed IL1 in normal unstimulated epidermis, 2) show that, compared to 7 internal organs, the epidermis contains the highest activity, 3) suggest that epidermal IL1 is mainly situated in the cytosol, 4) identify a MW approximately 17 Kd form with a pI 5.7, as well as a MW approximately 30 Kd form which might represent an IL1 precursor, 5) demonstrate the copurification of PGE2 and collagenase stimulatory and thymocyte comitogenic activity and 6) give a starting reference for the in vivo study of IL1 activity in pathologic situations.

Animals↗
PubMed1985

Cultured human epidermis cells produce cell-associated interleukin 1-like prostaglandin E2- and collagenase-stimulating factors.

In order to identify factors which may regulate the functions of dermal fibroblasts, cell lysates and conditioned media of cultured human epidermal cells were tested on dermal fibroblasts for the stimulation of prostaglandin E2- and collagenase-production. Both prostaglandin E2- and collagenase-stimulating activities appeared during epidermal cell culture: after 2 d they were detected in the cell lysate, and after 4 d of culture they were found also in the conditioned media. Molecular sieving chromatography of epidermal cell lysates led to the detection of two main peaks showing concomitant prostaglandin E2- and collagenase-stimulating activities at Mr approximately equal to 18 000 and Mr approximately equal to 10 000. A single peak of concomitant prostaglandin E2- and collagenase-stimulating activities were seen at Mr approximately equal to 10 000 in the epidermal cell conditioned media. This suggests that the cell-associated concomitant prostaglandin E2- and collagenase-stimulating activities are processed from a common precursor molecule and released. Collagenase-stimulating activity without accompanying prostaglandin E2 was also detected in the range of Mr approximately equal to 30 000-45 000.

Adolescent↗
PubMed1985

Immune response to Staphylococcus aureus in atopic dermatitis.

The skin of patients with atopic dermatitis (AD) is severely colonized with Staphylococcus aureus. Therefore, a study was conducted to assess some basic features of the S. aureus-specific immune response in patients with AD and healthy nonatopic individuals. Some particular features were found: a selective hyporesponsiveness to purified S. aureus cell walls (PCW) in delayed skin reactivity; half of our AD patients showed serum IgE to PCW and soluble S. aureus protoplast antigens; elevated PCW-IgE did not correlate with positive immediate skin reactions to whole S. aureus and their cell walls; regional lymphadenopathy but not impetiginization was associated with increased PCW-IgE and high total IgE. It is suggested that these changes in the immune response to S. aureus are related to the chronic S. aureus colonization of the skin.

Adolescent↗
PubMed1985

The immune response to S. aureus in atopic dermatitis.

The skin of patients with atopic dermatitis is heavily colonized with S. aureus, and their immune response to S. aureus shows some particular features: (1) A selective hyporesponsiveness to purified S. aureus cell walls in delayed type hypersensitivity skin reactions. (2) The presence of IgE to cell walls and soluble antigens of S. aureus in patients with high serum IgE levels. (3) Elevated cell wall IgE do not correlate with positive immediate skin reactions to whole S. aureus and their cell walls. (4) Regional lymphadenopathy but not impetiginization is associated with high total IgE and S. aureus cell wall IgE. We suggest that these changes in the immune response to S. aureus are related to the chronic S. aureus colonization of the skin.

Adult↗
PubMed1985

Staphylococcus aureus skin colonization in atopic dermatitis patients.

A study was conducted to compare the Staphylococcus aureus skin colonization of 21 patients with atopic dermatitis (AD) and 22 healthy controls. It was found that the total aerobe count (total CFU/cm2), the S. aureus fraction thereof and the S. aureus carrier frequency were significantly higher in apparently normal skin of AD patients than in healthy individuals. In addition, compared to normal skin of patients S. aureus density was 100 to 1,000 times higher in the 3 different kinds of lesional skin (dermatitic, lichenified and impetiginized sites). 190 S. aureus strains isolated from the skin of AD patients were tested for sensitivity to 5 topically used antibiotics and the results reported. Besides the biological consequences for the person affected by AD this severe colonization with S. aureus is of epidemiological importance. Several outbreaks of S. aureus infections by dispersal from dermatitic skin have been described. Therefore some preventive and therapeutic aspects are discussed.

Dermatitis, Atopic↗
PubMed1985

[Significance of skin colonization with Staphylococcus aureus in atopic dermatitis].

In patients with atropic dermatitis, skin of normal appearance as well as skin that has undergone pathological changes is heavily colonized by Staphylococcus aureus. Studies have determined certain factors that favor this colonization. The lesions show highly elevated S. aureus counts, resulting in further damage to the skin. This finding is supported by the fact that antibacterial treatment in combination with steroids is superior to steroids alone.

Anti-Bacterial Agents↗