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L Meunier

Publications and source records attributed to L Meunier.

At least 19 recordsLinked to original sources
PubMed1996

Quantification of CD1a, HLA-DR, and HLA class I expression on viable human Langerhans cells and keratinocytes.

In order to determine precisely the cellular density of surface molecules that are critical for antigen presentation in human epidermis, we utilized a quantitative immunofluorescence indirect assay and performed flow cytometric analysis of human epidermal cell (EC) suspensions. We first demonstrated that Tricolor-labeled streptavidin coupled to Cy-5 (SA-TC) was a reliable marker for non viable EC and that SA-TC+ EC accounted for the frequent nonspecific background of fluorescence due to isotype controls binding, although Langerhans cells (LC) and Keratinocytes (Kc) express Fc receptors for IgG on their surfaces. These results indicate that quantification of cell surface antigens on human EC requires the concomitant use of a marker of viability. Multicolor flow cytometric analysis allowed us to quantify CD1 molecules and major histocompatibility complex (MHC) antigens on viable human LC and Kc. Our results demonstrated a weak expression of MHC class I molecules on viable LC (163 +/- 19 x 10(3) molecules/cell) compared to viable Kc (785 +/- 110 x 10(3) molecules/cell). Mean antigen density of HLA-DR and CD1a molecules on viable LC were 579 +/- 82 x 10(3) molecules/cell and 1600 +/- 133 x 10(3) molecules/cell, respectively. Quantitative flow cytometry of viable EC may be proposed to evaluate the number of membrane antigens whose level of expression is related to cellular maturation or activation that occurs in skin diseases.

Adult↗
PubMed1996

[Cutaneous leishmaniasis].

Leishmaniasis is a group of parasitic conditions due to a flagella protozoan of the Leishmania genus and transmitted to man by phlebotomine sandflies. Cutaneous leishmaniasis exists all over the world. Those of the Old World are, in the vast majority of cases, purely cutaneous and spontaneously regress in several weeks to several months. In general, local treatment is sufficient. Those of the New World, due to multiple leishmaniasis complexes, involve a major risk of developing into a secondary mucosal form when rapid means of identifying the genus are not available. First-line treatment consists of antimony derivatives. In endemic regions, prophylaxy remains essential.

Humans↗
PubMed1996

In vivo retinoic acid modulates expression of the class II major histocompatibility complex and function of antigen-presenting macrophages and keratinocytes in ultraviolet-exposed human skin.

UNLABELLED: Because retinoic acid (RA) can alter photoaging of the skin and repeated ultraviolet (UV)-induced immunologic injury may play a role in chronic photoaging, we asked whether RA alters the acute photoimmunologic effects of UV radiation. Two sites from each volunteer were treated with 0.1% RA or vehicle continuously for 24 h before and 24 h after a 4-minimal erythema dose UVB exposure. RA did not function as a sunscreen, as determined by quantitating the increase in redness after 1 minimal erythema dose to vehicle- and RA-pretreated sites (n = 12). By flow cytometric analysis of epidermal cell suspensions harvested 3 d after the UV-EC, RA treatment did not protect CD1+ Langerhans cells from being depleted by UV light and did not modify the number of UV-induced infiltrating CD36+CD11b+CD1-DR+ macrophages. RA treatment did, however, result in a 40% downregulation of human leukocyte antigen (HLA)-DR expression on these infiltrating macrophages (p = 0.016) (n = 11), in conjunction with a decrease in alloantigen-presenting cell activity of RA-treated UV-EC as measured by T-cell proliferations. RA also induced a 72% inhibition of the autologous T suppressor-inducer cell proliferation induced by UV-EC (vehicle: 21,813 +/- 7,302 cpm; RA; 5,299 +/-635 cpm) (n = 3). The downregulation could be due to RA-modulated keratinocytes; RA-treated UV-EC keratinocytes depleted of CD1a+ and DR+ antigen-presenting cells displayed a greater ability, relative to similarly treated vehicle-EC keratinocytes, to inhibit alloantigen presentation. IN CONCLUSION: (i) in vivo RA treatment did not protect human Langerhans cells from being depleted by UV and did not block infiltration of macrophages into sunburned skin; and (ii) RA did decrease autologous and allogeneic T-cell reactivity induced by macrophage antigen-presenting cells in UV-exposed epidermis, at least in part by downregulating their HLA-DR expression and by upregulating inhibitory signals from UV-irradiated keratinocytes.

Adult↗
PubMed1996

Enhanced biological activity of antisense oligonucleotides complexed with glycosylated poly-L-lysine.

We sought to exploit glycosylated poly-L-lysine (pLK) to increase the uptake and biological antisense activity of a phosphorothioate oligonucleotide (pt-odn) [pt-odn complementary to the 3' noncoding region of intercellular adhesion molecule-1 (ICAM-1) (odn(ICAM-1))] complementary to the 3'-noncoding region of ICAM-1 in A549 cells. Dose-dependent inhibition of ICAM-1 expression was obtained (IC50 = 500 nM) through treatment of cells with odn(ICAM-1) complexed with pLK carrying fucose residues in the presence of 100 microM chloroquine. Alteration in the charge ratio between fucosylated pLK and pt-odn had a significant effect on the efficacy of inhibition (optimal conditions, charge ratio = 1.1). This effect was also dependent on the number of fucose moieties per pLK. Free pt-odn or pt-odn complexed with nonglycosylated pLK gave no inhibition at concentrations of < or = 2 microM. Two control pt-odn (one was targeted against an unrelated gene not present in these cells, gag(HIV), and the other had a randomized sequence) gave no inhibition of ICAM-1 expression in the presence or absence of pLK carrying fucose residues at concentrations of < or = 2 microM. When complexed with pLK carrying 100 fucose residues, the amount of cell-associated pt-odn was increased by 15-fold compared with the free pt-odn. Nongycosylated pLK also increased the amount of cell-associated pt-odn by >10 fold but did not alter the biological activity. These results demonstrate clearly the potential of glycosylated pLK as a pt-odn transporter.

Chloroquine↗
PubMed1995

Suppressor T cell-activating macrophages in ultraviolet-irradiated human skin induce a novel, TGF-beta-dependent form of T cell activation characterized by deficient IL-2r alpha expression.

Because UV-induced epidermal macrophages (UV-Mph) preferentially activate CD4+ T suppressor-inducer cells and induce tolerance, we hypothesized that they differentially up-regulate T cell early activation genes compared with constitutive epidermal APC, Langerhans cells. We used epidermal cells from UV-exposed (UV-EC) and control (C-EC) human skin to stimulate allogeneic CD4+ T lymphocytes. Reverse transcriptase-PCR revealed that both C-EC (Langerhans cells) and UV-EC (UV-Mph) induced 10(3)- to 10(6)-fold increases in IL-2 mRNA. However, while T cells stimulated by C-EC for 48 h showed a greater than 10(3)-fold increase in IL-2R alpha mRNA, those stimulated by UV-EC did not (n = 5, p = 0.004). Flow cytometry demonstrated that 4.1 +/- 2.3% of unstimulated CD4+ lymphocytes expressed cell surface IL-2R alpha, which increased to 15.7 +/- 1.8% upon stimulation by C-EC for 48 h, but stimulation by UV-EC failed to increase the IL-2R alpha+ population (n = 3, p = 0.038). The addition of neutralizing anti-TGF-beta Abs to UV-EC-stimulated cultures restored CD4+ cell surface IL-2R alpha expression to 12.9 +/- 0.2%. CD4+ T cell activation by UV-Mph is distinct from previously described models of tolerance such as Th2 activation (IFN-gamma mRNA was induced and IL-4 mRNA was not) and Th1 anergy (IL-2 mRNA levels induced by UV-EC and C-EC were similar). Furthermore, costimulatory signals were provided by UV-Mph; CTLA4-Ig and LFA-3-Ig fusion proteins and Abs to CD2, LFA-3, LFA-1, and ICAM-1 inhibited UV-Mph-induced T cell proliferation. Thus, the altered immune outcome induced by UV-Mph (tolerization) compared with Langerhans cells (sensitization) is reflected as a novel mechanism of initial CD4+ T cell early activation gene expression characterized by TGF-beta-dependent deficient IL-2R alpha expression.

Antigen-Presenting Cells↗
PubMed1995

In human dermis, ultraviolet radiation induces expansion of a CD36+ CD11b+ CD1- macrophage subset by infiltration and proliferation; CD1+ Langerhans-like dendritic antigen-presenting cells are concomitantly depleted.

Antigen-presenting (APC), suppressor T-cell-inducing macrophages infiltrate both human and murine epidermis after ultraviolet radiation (UVR) exposure. To determine their derivation, we prepared epidermal cell and dermal cell suspensions from human keratome biopsy specimens obtained from nonexposed skin and from UVB-irradiated sites (3 d after four times the minimal erythema dose). Simultaneous triple-marker flow cytometric analysis established the extended phenotype of macrophages infiltrating sunburned human epidermis (CD1a- CD1c- CD11b+ CD11c+ CD36+ Fc gamma RII+ DR+). This then enabled us to track dermal cells of this phenotype after UVR in relation to the heterogeneous DR+ populations in normal dermis. By both in situ immunohistology and cell suspension flow cytometry, UVR induced an expansion of bone marrow-derived DR+ cells in the perivasculature and sub-basement membrane zone of the papillary dermis. Despite an overall expansion of DR+ cells, the CD1a+ CD1c+ CD36- DR+ Langerhans-cell-like dendritic APC subset of dermal DR+ cells was depleted (p < 0.05), indicating that UVR-induced epidermal Langerhans cell loss (from 95% to 7% of DR+ epidermal cells) is not accounted for by Langerhans cell accumulation in the dermis. By contrast, UVR exposure induced a selective expansion of the dermal macrophage subset, which is phenotypically identical to the monocytic/macrophagic APCs that appear in the epidermis after UV injury (p < 0.01). Cell cycle analysis (to determine whether this expansion was accounted for entirely by infiltration) revealed no increase in the percentage of DR+ CD36+ UVR-exposed dermal cells in S/G2/M phase; however, the expanded DR+ CD36+ subset continued its already substantial level of proliferation unabated. Therefore, epidermal macrophages derive not only from transcapillary migration, but also from in situ proliferation of a dermal precursor. Taken together, these findings show that UVR creates an epidermal and dermal APC milieu which is dominated by monocytic/macrophagic cells, through depletion of cells of dentritic APC phenotype, and concomitant selective dermal expansion of a CD1a- CD1c- CD11b+ CD36+ Fc gamma RII+ DR+ (monocyte/macrophage) population.

Adult↗
PubMed1995

Differential responsiveness of Langerhans cell subsets of varying phenotypic states in normal human epidermis.

Epidermal Langerhans cell heterogeneity is poorly understood with regard to phenotypic characteristics, such as the expression of human leukocyte antigen (HLA)-DR, integrin, and Fc receptor molecules, as well as functional characteristics, such as the ability to process and present antigens or produce cytokines during various phases of immigration and maturation. Technical limitations of Langerhans cell number have limited functional assays on putative Langerhans cell subsets in in vivo epidermis. Therefore, we used flow cytometry for simultaneous phenotypic and functional assessment at the single-cell level within the Langerhans cell population. Freshly isolated human epidermal cell suspensions were stained with a battery of monoclonal antibodies, including anti-HLA-DR, -CD1a, -CD1c, -CD11c, -Fc gamma RII, and -Fc epsilon RI. Two distinct Langerhans cell subsets were identified by their different levels of HLA-DR expression. The DRHi subset expressed higher amounts of CD11c and exhibited greater cytoplasmic complexity and higher baseline calcium than the DRLo subset (p < or = 0.03 for each). Some subjects also expressed high levels of Fc epsilon RI in the DRHi, CD11cHi subset. To determine whether these phenotypic subsets may exhibit differential signal-transduction functional properties, Langerhans cells were partially enriched over Ficoll-Hypaque and their cytosolic mobilization after the addition of ionomycin was analyzed using the calcium indicator, indo-1, in conjunction with quantitative analysis of HLA-DR expression. By this real-time flow cytometric analysis, a new subpopulation was revealed within the DRLo Langerhans cell subset. This subset increased its cytosolic calcium concentration much more than the other two subsets (change in indo-1 blue:violet emission ratio of 37.33 +/- 2.34 in the Hi Flux DRLo subset versus 13.23 +/- 0.29 in the Lo Flux DRLo subset, and versus 7.6 +/- 2.99 in the Lo Flux DRHi subset). These data indicate that functional, as well as phenotypic, subsets of Langerhans cells exist within normal human epidermis. Their responses to physiologic stimuli may relate to maturational stage or the level of in vivo activation.

Adult↗
PubMed1995

[Multiple cutaneous carcinoma and chronic lymphoid leukemia].

INTRODUCTION: Skin cancer occurs more readily in more aggressive forms in immunodepressed subjects. We report the case of a patient with chronic lymphoid leukaemia and multiple skin carcinomas complicated with carcinomatous lymphangitis. CASE REPORT: A 63 year-old man with chronic lymphoid leukaemia, stage A in the Binet classification, had multiple epidermoid carcinomas on the trunk and face. The skin tumours were complicated with cervical lymph mode metastases, then a prethoracic carcinomatous lymphangitis with a rapidly fatal clinical course. DISCUSSION: Chronic lymphoid leukaemia and lymphomas are associated with a high incidence of skin carcinoma. The immunodepression inherent in the haematologic disease would appear to favor aggressive skin cancers. Our case was particularly severe since the carcinomatous lymphangitis was rapidly fatal.

Basal Cell Carcinoma↗
PubMed1995

[Lichen planus and hepatitis C virus. Apropos of 5 new cases].

Lichen planus is an immunologically mediated skin or mucous disease, which has recently been described in some patients with hepatitis C virus-related liver disease. We report 5 new cases of the association of hepatitis C with lichen planus, to be added to the 15 cases published in the literature. The sex ratio (female/male) was of 1.2. Lichen planus occurred more frequently in chronic active hepatitis (2/3 of cases) than in cirrhosis (1/3 of cases). Lichen planus manifestations were only mucous (30%), only cutaneous (40%) or both (30%). Mucous lesions were mainly observed in patients with cirrhosis (3/4 of cases). The onset of skin and hepatic manifestations was variable, with liver disease as the most frequent revealing symptom (60%). The influence of interferon remains unclear. However, it seemed to trigger more than to relieve lichen planus.

Adrenal Cortex Hormones↗
PubMed1995

[Primary cutaneous nocardia asteroides nocardiosis in an immunocompromised patient].

INTRODUCTION: Nocardiasis is caused by a germ belonging to the Actinomycetales order. Skin disease usually occurs as a secondary localization of a pulmonary infection in an immunocompromised patient. Purely cutaneous lesions usually occur in immunocompetent subjects. CASE REPORT: We observed primary cutaneous nocardiasis due to N. asteroides with a cold abscess in a patient with a pemphigoid given immunodepression treatment. DISCUSSION: Primary cutaneous nocardiasis can occur by direct contamination of a skin wound. In our patient with a pemphigoid given immunodepression treatment, the erosion of a pemphigoid bulla and general corticosteroid treatment favoured the localized infection. Cure could not be obtained until after 7 months treatment. This long course can be explained by the need to continue high-dose general corticosteroids to control the pemphigoid.

Aged↗
PubMed1994

CD11b+ macrophages that infiltrate human epidermis after in vivo ultraviolet exposure potently produce IL-10 and represent the major secretory source of epidermal IL-10 protein.

Because activated human macrophages can be potent sources of IL-10, and because immunosuppressive tolerance-inducing macrophages populate the skin after UV exposure, we determined whether IL-10 is induced after UV exposure of human skin and whether it is related to the immigrating macrophages. Keratomes were obtained from control skin or from skin obtained 72 h after a single exposure to four minimal erythemal doses of UVB. Quantitative reverse-transcriptase PCR on total RNA extracted immediately from skin keratomes showed that IL-10 mRNA was elevated in UV-exposed skin. Epidermal cell suspensions from non-UV-exposed keratomes (C-EC) and UV-exposed keratomes (UV-EC) were fractionated by sequential immunobead selection. IL-10 mRNA was reproducibly 200- to 400-fold higher in CD11b+ UV-EC (macrophages) relative to CD11b- UV-EC (keratinocytes). IL-10 mRNA was not detected in C-EC that contained the CD1a+ population (Langerhans cells) nor in CD1a- C-EC keratinocytes from normal skin. As determined by ELISA, CD11b+ UV-EC IL-10 cell-associated protein was fivefold higher than that of CD11b- UV-EC; this was confirmed by flow cytometric visualization of IL-10 protein in permeabilized cells. CD11b+ UV-EC macrophages secreted IL-10 protein into the supernatant at a level of 333 +/- 51 pg/10(6) cells, whereas UV-EC keratinocytes did not secrete detectable levels of IL-10 (n = 3), although UV did induce low levels of IL-10 mRNA and cell-associated protein in keratinocytes. Therefore, although human keratinocytes accumulate intracellular IL-10 after in vivo UV exposure, the most potent production and secretion of IL-10 in the epidermis seems to be that of UV-induced macrophages. Skin-infiltrating macrophage secretion of such a potent immunoregulatory cytokine may account for the delayed immunosuppressive environment of sunburned skin and the altered APC activity of the infiltrating macrophages.

Adult↗
PubMed1994

Retinoic acid upregulates human Langerhans cell antigen presentation and surface expression of HLA-DR and CD11c, a beta 2 integrin critically involved in T-cell activation.

Immunomodulatory effects of retinoids may be part of their anti-carcinogenic and anti-inflammatory properties. We studied the in vivo effects of retinoic acid (RA) on antigen-presenting activity of human epidermal Langerhans cells and on accessory cell activity of keratinocytes. Two skin sites from each volunteer were treated in vivo with 0.1% RA or vehicle, respectively, once a day for 4 d. RA-treated epidermal cell (RA-EC) alloantigen presentation to CD4+ T cells in each volunteer tested was consistently greater than that induced by vehicle EC. However, this increased antigen-presenting activity did not lead to autoreactive CD4+ T-lymphocyte proliferation. Elevated unfractionated epidermal antigen-presenting activity of RA-EC was not due to increased keratinocyte major histocompatibility complex (MHC) or intercellular adhesion molecule expression or to other keratinocyte accessory signaling, because incubation of CD1a-fluoroscence-activated cell sorter (FACS)-purified RA-EC inhibited alloantigen presentation, presumably through increased keratinocyte transforming growth factor-beta. By contrast, Langerhans cell function was upregulated; FACS-purified CD1a+ Langerhans cells derived from RA-EC displayed a markedly increased ability, relative to Langerhans cells from vehicle EC, to present alloantigen to T cells. Triple color flow-cytometric analysis of RA-EC and vehicle EC suspensions revealed that RA treatment did not modify the number of DR+ and CD1a+DR+EC, but did result in statistically significant increases in Langerhans cells expression of HLA-DR, CD11c, and CD1c. Another novel finding was that HLA-DR-dependent Langerhans cells antigen-presenting activity in both normal and RA-treated skin was completely blocked by anti-CD11c antibody. Thus, retinoid upregulation of antigen-presenting activity may be due to upregulation of Langerhans cell CD11c, as well as class II MHC. Upregulation of cutaneous immune responsiveness in human skin without autoreactivity has not (to our knowledge) been reported previously, and the Langerhans cell phenotypic and functional state achieved is distinct from previously reported states of Langerhans cell activation.

Antigen Presentation↗
PubMed1994

Acquired progressive lymphangioma.

Acquired progressive lymphangioma (APL) is a rare, benign proliferation of lymphatic capillary origin, which is characterized histologically by dermal vascular channels and a 'dissection of collagen' appearance. We describe a 30-year-old patient with an extensive, refractory APL on the right breast, which slowly developed over a period of 23 years. Pathologists and dermatologists should be aware of this entity, as early surgical treatment may be totally curative when the lesion is limited in size.

Breast Neoplasms↗
PubMed1994

[Scleroderma of the shoulders after treatment with combined bleomycin and radiotherapy].

INTRODUCTION: There are many causes of scleroderma. We observed a case of scleroderma involving the shoulder and neck area after combined bleomycin and radiotherapy. CASE REPORT: After six cycles of a CHOP-bleo protocol followed by radiotherapy for lymph node lymphoma, a female patient presented scleroderma involving the shoulders and neck area. Total bleomycin dose was 252 mg. DISCUSSION: Among the imputable factors, particularly extrinsic factors, in a series of 33 cases of different chemotherapy protocols published by Peters et al. in 1988, we retained the bleomycin radiotherapy administration sequence as the cause of this complication. Given after bleomycin, radiotherapy could increase the risk of scleroderma.

Adult↗