bromochloroacetic-acid and Dermatitis--Contact

The immunology of the epidermis has received considerable study over recent years. After the antigen-presenting capacity of epidermal Langerhans cells was confirmed, subsequent studies suggested that keratinocytes could modulate certain immunologic events through production of a cytokine, epidermal cell-derived thymocyte-activating factor (ETAF). Most recently, a murine epidermal cell population, the dendritic Thy-1-positive cell, has been shown to possess natural killer-cell-like activity. In this review, the biology of these cell types are discussed. A discussion of allergic contact hypersensitivity and its alteration by ultraviolet light is used to illustrate some of the complex control mechanisms that continue to be the subject of ongoing study.

Topics: Animals; Antibodies, Monoclonal; Antigen-Presenting Cells; Dermatitis, Contact; Epidermal Cells; Epidermis; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Immune Tolerance; Interleukin-1; Keratins; Langerhans Cells; T-Lymphocytes, Cytotoxic; Ultraviolet Rays

In all mammalian species so far examined, Langerhans cells or their precursors are the only epidermal cells expressing Ia antigens or their equivalents. In man, xeno-antisera raised in rabbits against purified B-lymphocyte cell membrane antigens were utilized to stain the Langerhans cells by either fluorescent or immunoferritin methods. As high proportion of the indeterminate cells in the epidermis also expressed HLA-DR antigens, and a relationship to Langerhans cells is suggested. Confirmation of these results was obtained in mouse. Alloantisera raised against I-A and I-EC subregion products again stained only Langerhans cells. Fluorescent, immunoperoxidase, and immunoferritin methods were used and confirmation of the specificity of the reaction was achieved at the electron microscope level. Langerhans cells were shown by ATPase staining to be absent from the epithelium of the central cornea, but present in the limbus. Population of the entire corneal epithelium surface was induced by application of irritants or contact sensitizing agents such as DNCB. Grafting of corneas either deficient or populated with Langerhans cells, to skin beds, may answer the question of the influence of such cells on allograft rejection.

Topics: Animals; Behcet Syndrome; Cattle; Cell Communication; Chickens; Chiroptera; Cricetinae; Dermatitis, Contact; Female; Guinea Pigs; Histiocytosis, Langerhans-Cell; Histocompatibility Antigens Class II; HLA Antigens; Humans; Keratins; Langerhans Cells; Lorisidae; Lymph Nodes; Lymphocytes; Mice; Mitosis; Mycosis Fungoides; Rabbits; Rats; Receptors, Immunologic; Sheep; Stomatitis, Aphthous; Swine; T-Lymphocytes; Thymus Gland

A 54-year-old woman had a 3 year history of a recurrent bilateral axillary rash during the summer months. Both axillae showed hyperkeratotic, fissured and cobblestone plaques. Skin biopsy showed the histology previously defined as axillary granular parakeratosis. This finding may indeed represent an unusual contact reaction to anti-perspirants interfering with epidermal keratinization.

Topics: Axilla; Biopsy; Deodorants; Dermatitis, Contact; Epidermis; Exanthema; Female; Humans; Keratins; Middle Aged; Parakeratosis; Recurrence; Seasons

We have previously reported 18 cases of an ichthyosiform contact dermatitis caused by antiseptic solutions containing 3% cetrimide and 0.3% chlorhexidine. The reaction was traced to cetrimide, a mixture of quaternary ammonium compounds that are widely used as disinfectants and detergents. Quaternary ammonium compounds are known irritants. To elucidate the pathogenesis of the abnormal keratinization caused by cetrimide, electron microscopy was performed on biopsied lesions from five patients and on specimens from rabbits in which a mild reaction had been induced by closed patch with Savlon, cetrimide, and chlorhexidine. The patients' samples revealed hyperkeratosis with striking vesiculation of lamellar bodies in the granular cells and upper spinous cells, premature secretion of lamellar bodies, and abundant remnants of lamellar bodies and retention of desmosomes between the corneocytes. Similar lamellar bodies changes were induced in rabbit skin after 48 hours of closed patch with Savlon 1:30 and cetrimide 0.1%, but not with chlorhexidine 3%-further indication that cetrimide was the cause of the dermatitis. We conclude that the abnormal keratinization can be attributed, at least in part, to dysfunction of lamellar bodies resulting from the direct effects of cetrimide on the lipids and enzymes of lamellar bodies. Vesiculation with dysfunction of lamellar bodies may be an important pathogenetic mechanism in irritant dermatitis caused by quaternary ammonium compounds.

Topics: Animals; Anti-Infective Agents, Local; Anti-Inflammatory Agents, Non-Steroidal; Blister; Cetrimonium; Cetrimonium Compounds; Chlorhexidine; Cytoplasmic Granules; Dermatitis, Contact; Dermatitis, Irritant; Desmosomes; Drug Combinations; Epidermis; Humans; Ichthyosis; Keratinocytes; Keratins; Keratosis; Lipid Metabolism; Microscopy, Electron; Organelles; Patch Tests; Rabbits; Skin

Topics: Animals; Autoantibodies; Dermatitis, Contact; Dogs; Female; Guinea Pigs; Humans; Immunohistochemistry; Keratins; Male; Psoriasis; Rabbits; Skin

Diphenylcyclopropenone (DCP) was applied to the upper arms of five alopecia areata patients using 10% of the concentration that had been applied previously to the scalp during topical immunotherapy. DCP applied in this concentration evoked a mild eczematous reaction. Biopsies were taken before DCP application and after 24, 48 and 96 h. A large increase in T-lymphocytes and CD14-positive cells in the dermis was seen after 24 h. Migration of these cells into the epidermis was mainly observed during the first 48 h. This was followed by epidermal proliferation as assessed by the number of Ki-67-positive nuclei and the degree of Ks8.12-binding. Both showed their main increase after 48 h; but after 24 h the increase of Ki-67-positive nuclei was significant (P < 0.04). Involucrin and filaggrin showed a gradual increase which became substantial after 96 h (both P < 0.04). As the invasion of inflammatory cells into the epidermis preceded the main increase in epidermal proliferation, cytokines are suggested as possible mediators for the initial phase of the proliferative response after DCP application.

Topics: Cell Division; Cyclopropanes; Dermatitis, Contact; Epidermis; Female; Filaggrin Proteins; Humans; Keratins; Male; Skin

In previous experiments, pretreatment of CD-1 mouse skin with prostratin (12-deoxyphorbol 13-acetate) inhibited hyperplasia, induction of ornithine decarboxylase and edema in response to acute treatment with phorbol 12-myristate 13-acetate (PMA). We report here that prostratin inhibits biological responses induced by multiple (chronic) PMA treatment. A typical chronic treatment schedule consisted of five applications of 3.2 nmol (2 micrograms) PMA at 48 h intervals. Most effective inhibition could be achieved when the first PMA treatment was preceded 48 h before by a lower dose of prostratin (256 nmol = 100 micrograms) and each PMA treatment was preceded 15 min before by a higher dose (2.56 mumol = 1 mg) of prostratin. Under this schedule hyperplasia was completely blocked, as was keratin K6 expression (a marker of hyperproliferative epidermis), whereas myeloperoxidase activity (a marker of neutrophil granulocyte infiltration) was reduced to 36%. 12-Deoxyphorbol 13-phenylacetate (dPP), a non-promoting 12-deoxyphorbol derivative that binds to protein kinase C with two orders of magnitude higher potency than does prostratin, showed the same pattern of inhibition as did prostratin for a single PMA treatment but with a corresponding two orders of magnitude higher potency. In the case of chronic PMA treatment, however, dPP failed to inhibit hyperplasia fully, though it reduced keratin K6 expression and inflammation. Dissociation of K6 expression from hyperplasia was unexpected, since expression of these two responses was thought to be closely coupled. We conclude that 12-deoxyphorbol 13-monoesters are functional antagonists for a class of protein kinase C-mediated responses closely correlated to tumor promotion.

Topics: Animals; Dermatitis, Contact; Drug Antagonism; Enzyme Induction; Hyperplasia; Keratins; Mice; Ornithine Decarboxylase; Peroxidase; Phorbol Esters; Skin; Tetradecanoylphorbol Acetate

Cod Gadus morhua and bovine trypsin degraded human epidermal keratin with similar efficacies in vitro around optimal pH, which was at pH 8.4 for cod trypsin and at pH 9.5 for bovine trypsin. Extract of intestines of cod, Atlantic herring Clupea harengus, Atlantic salmon Salmo salar, and redfish Sebastes marinus degraded keratin with similar efficacies with pH optima between 8.5 and 9.5. Sheets of plantar callus were degraded with somewhat lower efficacy than keratin. The keratin-degrading activity of extract of cod intestines had a temperature optimum around 45 degrees C. Inhibition with benzamidine and 4-phenylbutylamine showed that trypsin amounted to more than 2/3 of the keratin-degrading activity in all extracts of fish intestines. Apart from cod intestines, which had the lowest chymotrypsin content, chymotrypsin made a smaller but significant contribution to the keratin-degrading activity. The present investigation demonstrates that fish trypsin and extract of fish intestines are effective in degrading human epidermal keratin in vitro, and in a recent investigation the same was shown with fish pepsin. This may suggest a possible mechanism for the development of irritative contact eczema caused by exposure to fish.

Topics: Animals; Chymotrypsin; Dermatitis, Contact; Epidermis; Fishes; Hydrogen-Ion Concentration; In Vitro Techniques; Intestines; Keratins; Protease Inhibitors; Tissue Extracts; Trypsin

We have used monoclonal antibodies to study the expression of calgranulins by keratinocytes in inflammatory dermatoses. Calgranulins are intracellular calcium binding proteins which have inflammatory cytokine activity and are composed of at least two different chains, calgranulin A and B. Antibody CF 145 and CF 557 identify calgranulin A and B, respectively. MAC 387 recognizes a molecule probably containing both calgranulins. Keratinocytes in normal skin did not contain these molecules. The keratinocytes in 52 cases of different inflammatory dermatoses showed expression of both calgranulin chains in lesional but not in non-lesional skin. Keratinocytes in inflammatory dermatoses therefore express an intracellular calcium binding protein which has cytokine activity.

Topics: Antibodies, Monoclonal; Calcium-Binding Proteins; Calgranulin A; Calgranulin B; Dermatitis, Contact; Epidermis; Graft vs Host Disease; Humans; Keratins; Psoriasis; Skin Diseases, Vesiculobullous

A simple assay measuring degradation of human epidermal keratin and bovine tendon collagen is presented. Insoluble protein substrate (30 mg) was incubated with 1 ml buffer and enzyme sample for 1 h at 37 degrees C, following addition of 1 ml distilled water and removal of the remaining substrate by filtration/centrifugation. The protein content was determined in the filtrate/supernatant by the Lowry method. Keratin was prepared as follows: Freeze-drying, homogenization in a mortar or beetling mill, extraction in 0.9% (w/v) NaCl followed by water and 100% ethanol, drying at 37 degrees C. The assay was tested with pig pepsin, bovine trypsin, and crude extract of fish stomach, demonstrating that these preparations are effective in degrading human epidermal keratin.

Topics: Animals; Cattle; Collagen; Dermatitis, Contact; Epidermis; Fishes; Humans; In Vitro Techniques; Keratins; Peptide Hydrolases; Tendons

Immune response-associated (Ia) antigens are important as molecules in antigen recognition by T cells. Keratinocytes can express Ia antigens in many inflammatory dermatoses and by action of gamma interferon (IFN-gamma). A keratinocyte cell line, Pam 212 cells, expressed Ia antigens at maintaining culture. They also expressed Ia antigens under the influence of IFN-gamma. Liposomes carrying molecules from trinitrophenylated-Pam cells did not stimulate lymphnode cells (LCs) of contact sensitivity; however, liposomes carrying a large amount of those molecules stimulated LCs. This stimulation was attributable to contaminated Ia antigens in those molecules. Liposomes with a small amount of those molecules or trinitrophenylated-proteins from Pam cells were prepared. Into them were inserted Ia antigen-rich proteins from Pam cells, spleen cells, IFN-gamma-treated Pam cells, or epidermal cells containing Langerhans cells. Thus prepared liposomes stimulated the LCs significantly. The Ia antigens obtained from IFN-gamma-treated Pam cells worked as well as Ia antigens from epidermal cells that contained Langerhans cells as the molecule of antigen presentation in contact sensitivity.

Topics: Animals; Antigen-Presenting Cells; Cell Line; Dermatitis, Contact; Epidermal Cells; Epidermis; Histocompatibility Antigens Class II; Interferon-gamma; Keratins; Liposomes; Lymph Nodes; Lymphocyte Activation

Epidermal patterns of class II human lymphocyte antigen (HLA) expression in atopic and allergic contact dermatitis have been compared, using monoclonal antibodies recognizing each subregion. Expression of class II human lymphocyte antigens on keratinocytes has been confirmed in allergic contact dermatitis, while we have found them to be absent in atopic dermatitis. This finding argues that cell-mediated immune responses, possibly to epicutaneous contact with allergen, are not implicated in the pathogenesis of atopic dermatitis.

Topics: Adult; Antibodies, Monoclonal; Dermatitis, Atopic; Dermatitis, Contact; Epidermal Cells; HLA-D Antigens; Humans; Keratins

In normal murine epidermis Thy-1 antigen is known to be strongly expressed on a dendritic population of bone marrow derived cells lacking Ia antigens and faintly on keratinocytes. We now report on the induction of pronounced expression of Thy-1 antigen on keratinocytes by immunological stimuli as well as by chemical irritation and wounding. In contrast the induction of Ia antigens on keratinocytes is more restricted. It has been suggested that the dendritic Thy-1+ cells can suppress an immune response initiated by Ia antigen expressing Langerhans cells. The balance within epidermis between up- and down-regulation of immune reactions, may be even more complex if also keratinocytes expressing Thy-1 and/or Ia antigens should prove to participate.

Topics: Animals; Antigens, Surface; Dermatitis, Contact; Dinitrofluorobenzene; Epidermal Cells; Epidermis; Histocompatibility Antigens Class II; Immunoenzyme Techniques; Keratins; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Thy-1 Antigens

Leu-8 is a novel antigen expressed by the majority of mature T cells and certain other cells. Recent studies of the allogeneic mixed leukocyte reaction indicate that both Leu-8+ and Leu-8- subsets of Leu-3+ T cells have important functions in cell-mediated immunity in vitro. In order to determine whether Leu-3+8+ and/or Leu-3+8- T cells are present in cell-mediated immune reactions in vivo, we studied the immunohistology of allergic contact dermatitis in 8 biopsies from 8 patients with positive patch tests and 3 biopsies from 2 patients with Rhus dermatitis. Both Leu-3+8+ and Leu-3+8- T cells were present in each biopsy. Only 1 case had a definite minority of the Leu-3+8+ subset. These results suggest that, analogous to in vitro systems, both Leu-8+ and Leu-8- subsets of Leu-3+ T cells are involved in cell-mediated immunity in vivo. HLA-DR+ keratinocytes were present in only 3 of 11 biopsies at days 3-7. No HLA-DQ+ keratinocytes were identified. We also confirmed prior findings that Leu-3+ cells are the predominant T-cell population, Langerhans cells are increased, and B cells and NK cells are rare. Furthermore, Tac and Ki-67 expression by T cells and Leu-3 expression by Langerhans cells tended to increase over time.

Topics: Adolescent; Adult; Dendritic Cells; Dermatitis, Contact; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunologic Techniques; Keratins; Macrophages; Middle Aged; Phenotype; Receptors, Immunologic; Receptors, Interleukin-2; Skin; T-Lymphocytes

Human keratinocytes were investigated for the presence of single cilia. Almost all basal keratinocytes were found to carry a single cilium in normal, occluded, and psoriatic skin. The ciliary structure was progressively reduced in keratinocytes approaching the surface. No remnants of the ciliary apparatus were found in the granular layer. In one case of nickel-allergic dermatitis (patch test), the keratinocytes had lost their cilia; the significance of this surprising finding remains to be elucidated.

Topics: Adult; Cilia; Dermatitis, Contact; Epidermal Cells; Epidermis; Humans; Keratins; Microscopy, Electron; Nickel; Psoriasis

We have used tritiated thymidine (3HT) labelling and immunoperoxidase staining of 67 K polypeptide in human epidermis to study normal skin before and after irritation induced by application of croton oil (20% and 50% in olive oil). By this double labelling method, it was possible to identify, on the same skin section, DNA-synthesizing nuclei and epidermal cells which contained 67 K polypeptide. Our results clearly indicate that the germinative compartment of normal epidermis is a mixed population comprising basal and adjacent suprabasal cells; as a rule, absence of expression of 67 K polypeptide, which characterizes all basal cells, could not be regarded as a good marker to distinguish the germinative from the differentiating compartments. In mild primary irritation, the ratio of 3HT-labelled undifferentiated cells to keratinizing ones was similar to that observed in normal epidermis. In severe irritation, this homeostatic process was altered, as 3HT-labelled cells were mainly 67 K negative.

Topics: Aged; Cell Division; Croton Oil; Dermatitis, Contact; DNA; Female; Humans; Keratins; Male; Peptides; Skin

Topics: Dermatitis, Contact; Epidermis; Humans; Intercellular Junctions; Keratins; Langerhans Cells; Lymphocytes

The reaction in epidermal keratinocytes in sensitized and non-sensitized, normal guinea pigs after dichromate exposure has been investigated by electron microscopy. The results of the investigation show that the morphological alterations in keratinocytes in irritant and contact allergic reactions to dichromate are of a nonspecific nature. This underlines the fact that morphological reactions in the keratinocyte are uniform. The reactions were dose- and time-dependent. The morphology of the contact allergic reaction to dichromate in the guinea pig is consistent with that described for DNCB.

Topics: Animals; Chromates; Dermatitis, Contact; Dose-Response Relationship, Drug; Epidermal Cells; Epidermis; Guinea Pigs; Immunization; Keratins; Male; Microscopy, Electron; Potassium Dichromate; Time Factors

Topics: B-Lymphocytes; Dermatitis, Contact; Female; Fluorescent Antibody Technique; HLA Antigens; Humans; Isoantigens; Keratins; Langerhans Cells; Melanocytes; Molecular Weight; Skin

Electronmicroscopical investigation on 12 cutaneous biopsies of different localisation showed that the seborrhoic dermatitis is not comparable to a psoriatic tissue-reaction. Both, the cyto-morphological feature and the demonstrated localisation of the acid phosphatase are distinctly different from that of the psoriatic epidermis. The described changes are clearly more similar to the well known ultrastructural pictures of eczemateous reactions. In spite of the "eczema-like" ultrastructural picture seborrhoic dermatitis apparently can be separated from the allergic and irritant contact-dermatitis. Nevertheless, the epidermal alterations are also similar to chronic nummular eczema. They therefore are unspecific and do not allow any conclusion regarding the etiopathogenesis or nosological classification of this skin disease.

Topics: Acid Phosphatase; Basement Membrane; Cell Nucleus; Dermatitis, Contact; Dermatitis, Seborrheic; Desmosomes; Eczema; Endoplasmic Reticulum; Histocytochemistry; Humans; Keratins; Organoids; Phagocytes; Psoriasis; Skin; Vacuoles

Topics: Aniline Compounds; Biopsy; Dermatitis, Contact; Gold; Humans; Inclusion Bodies; Keratins; Lysosomes; Mercury; Microscopy, Electron; Mitochondria; Skin; Skin Absorption; Staining and Labeling