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Biomedical subjects

H K Muller

Publications and source records attributed to H K Muller.

At least 73 records · Page 4Linked to original sources
PubMed1989

Retinoic acid protects Langerhans' cells from the effects of the tumour promotor 12-O-tetradecanoylphorbol 13-acetate.

Retinoic acid prevents the decrease in epidermal Langerhans' cell (LC) density which occurs upon application of the tumour promotor 12-O-tetradecanoylphorbol 13-acetate (TPA) to murine skin. This occurred very rapidly, after only 1 week, and was still observed after 4 weeks of treatment. Retinoic acid alone increased the LC density, indicating that it could affect LC density independently of TPA. The induction of a contact sensitivity response which was inhibited by prior treatment with TPA due to the low LC density was also protected by retinoic acid. The anti-carcinogenic activity of retinoic acid is partially the result of its ability to inhibit tumour promotion. The loss of LC may be one of the important steps in tumour promotion as this would allow developing tumours to escape immune destruction. Our studies suggest that the ability of retinoic acid to suppress tumour promotion may be in part by protecting local antigen-presenting cells, thus allowing an immune response to be generated against tumours.

Animals↗
PubMed1988

Antigen presented in the local lymph node by cells from dimethylbenzanthracene-treated murine epidermis activates suppressor cells.

Application to skin depleted of LC by treatment with the chemical carcinogen DMBA of a dose of contact sensitizer optimal for inducing contact sensitivity activates transferrable suppressor cells. Excision of solvent- or DMBA-treated skin at various times following application of the contact sensitizer DNFB indicated that the fraction of antigen which leaves the skin within the first few hours induces tolerance. An initial signal inducing unresponsiveness, observed within 1/2 hr, was overturned 3-6 hr later. A more permanent tolerogenic signal in the DMBA- but not solvent-treated lymph node resulted from an epidermal cell from DMBA-treated skin presenting antigen to suppressor cells. Therefore it is likely that suppressor cells are activated in DMBA-treated mice by an epidermal cell which migrates to the local lymph node. Local lymph node cells from DMBA-treated mice also have a diminished ability to present antigen in vivo but they do not activate suppressor cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Suppressor cell activation and enhanced skin allograft survival after tumor promotor but not initiator induced depletion of cutaneous Langerhans cells.

During chemical carcinogenesis Langerhans cells (LC) are depleted from the epidermis, disrupting the normal immunological functions of the skin. Tumor promotors but not initiators, have been shown to deplete adenosine triphosphatase (ATPase)-positive LC from the skin and therefore the cutaneous immune system may be impaired during tumor promotion but not initiation. The present study shows that the tumor promotor 12-O-tetradecanoylphorbol 13-acetate (TPA) but not the initiator urethane depletes Ia-positive LC from BALB/c murine ear epidermis, and beta-glucuronidase-positive LC from C57BL mouse tail skin. Sensitization with 2,4-dinitrofluorobenzene (DNFB) through urethane-treated skin resulted in a normal contact sensitivity response when the mice were challenged 5 days later. In contrast, tolerance resulted from sensitization through TPA-treated skin as a result of the generation of suppressor cells. In addition, TPA but not urethane-treated C57BL mouse tail skin survived for an extended time when grafted onto histoincompatible BALB/c mice. Therefore, impairment of the normal immunological functions of skin resulted from treatment with the tumor promotor TPA but not the tumor initiator urethane, which suggests that a loss of LC during tumor promotion may impair immunological protection against skin tumors.

Animals↗
PubMed1988

Histamine-binding lymphocytes as a measure of reactivity to bee venom.

Reduced lymphocyte histamine-binding after in vitro exposure of whole blood samples to bee venom appears related to allergen reactivity. The reactivity demonstrated using this method matched the clinical findings and was used to monitor declining responses to allergen during desensitization therapy for hypersensitivity to bee venom. After successful desensitization to bee venom, patients' lymphocytes did not show decreased histamine binding following in vitro exposure to venom. We conclude that lymphocyte histamine-binding sites are down-regulated by allergen-mediated histamine release in hypersensitive subjects, and that this response diminishes with immunotherapy. This report describes a novel method for the in vitro assessment of reactivity to bee venom.

Bee Venoms↗
PubMed1988

Glomerulonephritis in the acute phase of Ross River virus disease (epidemic polyarthritis).

Hematuria and proteinuria were detected at the peak of symptoms in a case of Ross River virus (RRV) disease. No other infective cause was identified. A renal biopsy 28 days after the onset of nephritis showed mild mesangial proliferative changes and one segmental sclerotic lesion. Immunofluorescence showed widespread linear deposition of IgG in glomerular capillary walls with similar but weak staining for IgM, complement (C3) and fibrinogen; granular deposits of IgM and C3 in several arterioles; and IgM in a few mesangial cells. No electron-dense deposits were detected, nor was RRV antigen found in the renal tissue. Anti-glomerular basement membrane antibodies were not detected in the serum. Recovery from the renal disturbance was complete within three months although rheumatic symptoms persisted for 30 months.

Acute Disease↗
PubMed1987

Sensitization through carcinogen-induced Langerhans cell-deficient skin activates specific long-lived suppressor cells for both cellular and humoral immunity.

Application of 2,4-dinitrofluorobenzene (DNFB) to BALB/c mouse skin depleted of epidermal Langerhans cells (LC) by the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) activated cells which suppress both contact sensitivity and antibody production when transferred into naive host mice. Tolerance was induced by a concentration of DNFB optimal for inducing contact sensitivity in solvent-treated control mice. The cellular and humoral responses of hosts to a second antigen, 2,4,6-trinitrochlorobenzene (TNCB), were unaffected by these suppressor cells, demonstrating specificity for DNFB. Suppressor cells for cellular and humoral immunity could still be demonstrated 6 months following activation, by which time some mice had died, presumably of old age. The dose responses to sensitizer for generation of cells which suppressed contact sensitivity and antibody production differed, indicating that separate populations of suppressor cells probably inhibit these responses. Hence, during cutaneous chemical carcinogenesis, depletion of LC may allow activation of specific long-lived suppressor cells capable of inhibiting cellular or humoral antitumor immune responses.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Effects of low or high doses of short wavelength ultraviolet light (UVB) on Langerhans cells and skin allograft survival.

Since Langerhans cells (LC) are normally the only cells within the epidermis to express the class II major histocompatibility complex (MHC) transplantation antigens, depletion of LC could be expected to prolong skin allograft survival by reducing the antigenic disparity between host and recipient. To assess this hypothesis, donor C57BL mouse shaved dorsal trunk or tail skin was exposed to high (200 mJ/cm2) or low (40 mJ/cm2) doses of short wavelength ultraviolet light (UVB) before grafting on to the thorax of BALB/c mouse recipients of the same sex. These strains have different major and minor transplantation antigens. The effects of UVB treatments on LC were determined by electronmicroscopy. Skin grafted 1-14 days following a single high dose of UVB irradiation was ultrastructurally depleted of LC and survived significantly longer than unirradiated skin before being rejected. After a 21-day interval between exposure and grafting when LC were again present in the epidermis there was no significant difference between treated and control graft survival. Exposure to low dose UVB irradiation only significantly increased graft survival for skin transplanted 1-3 days after irradiation; skin grafted 4 days following irradiation survived for a similar period to unirradiated control skin grafts. Electronmicroscopy showed that the low UVB dose did not deplete LC from the epidermis. We conclude that after low dose UVB treatment the class II MHC antigens on the LC plasma membrane were lost temporarily, thus prolonging graft survival, but when the plasma membrane antigens were re-expressed graft survival returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Langerhans cell presentation of sheep red blood cells induces antibody production.

Mouse epidermal Langerhans cells (LC) were found to be capable of presenting sheep red blood cells (SRBC) to immune spleen lymphocytes, resulting in antibody production as assessed by a direct plaque cell assay. Spleen lymphocytes, prepared by removal of adherent cells, were unable to respond to SRBC in a 5-day culture; however, when co-cultured with either epidermal cells or splenic adherent cells, a response to SRBC occurred, as demonstrated by an increase in the number of antibody-producing cells. The LC were shown to be the antigen-presenting cells in these cultures, as depletion of LC via their Fc receptors abrogated the response. A similar reduction in the number of epidermal LC added to cultures likewise failed to induce antibody production. These experiments demonstrate that LC are able to present complex cellular antigens to the immune system, resulting in a B lymphocyte response.

Animals↗
PubMed1987

Enhanced survival of skin grafts depleted of Langerhans' cells by treatment with dimethylbenzanthracene.

Langerhans' cells (LC) are the only subpopulation of epidermal cells to express the class II major histocompatibility (MHC) glycoproteins (H-2 Ia in the mouse) under normal conditions. Since these antigens are important in the initiation of allograft rejection, the effect of LC depletion on mouse skin graft survival was studied. Treatment with the chemical carcinogen 9, 10-dimethyl-1,2-benzanthracene (DMBA) was observed to deplete LC from the epidermis on ultrastructural examination. DMBA-treated C57BL dorsal trunk or tail skin grafted onto BALB/c recipients had a prolonged survival compared to solvent-treated donor skin. This was observed 1 week after a single DMBA treatment; successive once-weekly treatments or three treatments within 1 week failed to enhance allograft survival further. Tail-skin grafts had consistently longer survival times in comparison to dorsal trunk-skin grafts, for both control and treated skin. Treatment of dorsal trunk or tail skin with DMBA probably enhanced skin graft survival on allogeneic recipients by causing a loss of LC, and therefore of the class II MHC antigens from the graft. To confirm this, congenic mouse strains were used: B10.A(2R) x B10.A differing only at H-2D, and B10.A(2R) x B10.A(4R) differing only at H-2 I-E. Treatment of B10.A(2R) tail skin with DMBA for 1 week did not affect its survival when grafted onto H-2D-disparate B10.A mice, whereas when grafted onto H-2I-E-disparate B10.A(4R) hosts the DMBA-treated grafts were not only accepted permanently, but induced specific unresponsiveness. This confirms that the DMBA-induced enhancement of graft survival was the result of a loss of H-2 Ia antigens, and therefore of LC from the treated graft.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Induction of tolerance via skin depleted of Langerhans cells by a chemical carcinogen.

Since treatment of mouse skin with the chemical carcinogen 7,12-dimethylbenz[alpha]anthracene (DMBA) substantially decreases the density of cutaneous Langerhans cells (LC), the immune status of mice sensitized to 2,4-dinitrofluorobenzene (DNFB) through DMBA-treated skin was investigated. Mice did not develop contact sensitivity to DNFB when applied to DMBA-treated dorsal trunk skin, whereas sensitization resulted when DNFB was applied to untreated abdominal wall skin. Mice immunized with DNFB via DMBA-treated skin did not respond to subsequent immunization through untreated dorsal trunk skin, demonstrating the generation of suppressor cells which could inhibit the activation of effector lymphocytes. Adoptively transferred spleen cells from mice immunized with DNFB through DMBA-treated skin inhibited the response of sensitized hosts, indicating the presence of efferently acting suppressor cells which could inhibit the function of effector lymphocytes. This study has demonstrated that sensitization via skin depleted of LC by chemical carcinogen treatment induces an active state of tolerance rather than immunity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

New methodology for assessment of the Langerhans cell network.

A new procedure is described for staining Langerhans cells (LCs) based on the ability of anti-S-100 antibody to stain both epidermal LCs and melanocytes, while L-Dopa stains only melanocytes. This procedure can be used on paraffin-embedded skin sections and is therefore advantageous for examination of pathological skin specimens. In order to determine how best to quantitate LCs in skin sections the distribution of LCs has been investigated using an improved method for preparation of epidermal sheets from mouse skin. Epidermal LCs stained for their surface membrane-bound enzyme adenosine triphosphatase were observed to link with each other via their dendrites, forming a single cell layer which undulates throughout the epidermis. It is therefore proposed that LCs in skin sections should be enumerated per unit length, after identification in paraffin-embedded sections double stained with anti-S-100 antibody and L-Dopa.

Adenosine Triphosphatases↗
PubMed1986

Quantitative assessment of Langerhans' cells in human cervical intraepithelial neoplasia and wart virus infection.

Langerhans' cell density was assessed quantitatively in cervical wart virus infection (cervical condyloma), cervical intraepithelial neoplasia, and koilocytic dysplasia with use of an antibody to S100 protein and an indirect immunoperoxidase technique. When compared with normal ectocervix, Langerhans' cell density was significantly decreased in cervical wart virus infection and significantly increased in cervical intraepithelial neoplasia. In koilocytic dysplasia, intermediate Langerhans' cell densities were obtained. In addition to being increased within the lesions of cervical intraepithelial neoplasia, Langerhans' cell density was increased in the adjacent normal ectocervix. Human papillomavirus, by reducing intraepithelial Langerhans' cell density, may decrease local immune surveillance and thus have a promoter effect in the development of cervical cancer. Following the development of cervical intraepithelial neoplasia the increase in intraepithelial Langerhans' cell density suggests a specific immune response directed against neoantigens associated with malignant transformation. If a permissive wart virus infection persists after transformation to cervical intraepithelial neoplasia (koilocytic dysplasia), continued depletion of Langerhans' cells results in intermediate densities.

Biopsy↗
PubMed1986

Reduction in murine Langerhans cell ATPase staining following topical but not systemic treatment with steroid and non-steroid immunosuppressants.

The effects on murine Langerhans cells (LC) of steroid and non-steroid immunosuppressive drugs which are commonly used for long-term immunotherapy of human patients were investigated. Hydrocortisone, prednisolone, cyclosporin A or azathioprine was administered daily for 7 consecutive days either topically by application to the skin, or systemically by intraperitoneal injection. LC densities were determined on the day following cessation of treatment by staining for the plasma membrane-bound enzyme adenosine triphosphatase (ATPase). All immunosuppressants caused a significant reduction in ATPase-positive LC when administered topically, but not systemically. The systemically administered drugs, although given in high concentration, may not have penetrated the epidermis in sufficient concentrations to disrupt the LC membrane. These observations are consistent with long term immunosuppressants depleting cutaneous LC by bone marrow suppression rather than by a direct effect on LC.

Adenosine Triphosphatases↗
PubMed1986

Analysis of histamine-binding lymphocytes in atopy.

Using flow cytofluorimetry, the histamine-binding properties and T cell subclass distribution of peripheral blood lymphocytes in normal and atopic subjects were investigated. In the case of active (or symptomatic) atopy, the levels of histamine-binding lymphocytes were significantly reduced. However, none of these parameters distinguished between normal individuals and patient groups when the atopics were asymptomatic except the OKT3 marker; in the atopic group, the proportion of OKT3-positive cells was lower. These results indicate that the decreased levels of histamine-binding lymphocytes in atopy are a secondary phenomenon, and that the ratio of T helper to T suppressor/cytotoxic cells is not significantly altered in atopic patients. The changes in histamine-binding lymphocytes appear to be unrelated to the decreased numbers of OKT3-positive cells, since the latter changes were evident in active and asymptomatic atopics.

Antibodies, Monoclonal↗
PubMed1986

Quantitative assessment of Langerhans cells in actinic keratosis, Bowen's disease, keratoacanthoma, squamous cell carcinoma and basal cell carcinoma.

The quantitative distribution of Langerhans cells (LC) was studied in a range of pre-neoplastic, in-situ and invasive neoplastic skin lesions using an antibody to S100 protein and the indirect immunoperoxidase technique. LC numbers were increased within the lesions of actinic keratosis, Bowen's disease, keratoacanthoma, squamous cell carcinoma and basal cell carcinoma. In all lesions except actinic keratosis the LC density was also significantly increased in the adjacent non-neoplastic epithelium. The increased LC density in neoplastic epithelium suggests either that LC are being retained within the abnormal epithelium for longer periods of time than normal or that increased numbers of LC are being actively attracted by factors produced by the neoplastic epithelium. While reduction of intraepithelial LC density may allow the initiation of neoplasia the increased density observed in this study suggests that at later stages of tumour growth LC may have a functional role in the host response to cutaneous neoplasia.

Bowen's Disease↗