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  • 1
    ISSN: 1600-0560
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 9 (2000), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The etiology and pathogenesis of psoriasis – one of the most common chronic, inflammatory, hyperproliferative skin disorders of man – have long fascinated dermatologists, pathologists and biologists alike. Here, we have a model disease that offers to study neuroectodermal-mesenchymal interactions in the widest sense possible. Epithelial, endothelial, and hematopoietic cells as well as neurons projecting into the skin apparently all interact with each other to generate the characteristic psoriatic lesion. For decades, the ongoing controversy on the molecular nature, choreography and hierarchy of these complex interactions e.g. between epidermal keratinocytes, T cells, neurotrophils, endothelial cells and sensory nerves has served as a driving force propelling investigative dermatology to ever new horizons. This debate has not only been at the heart of our quest to develop more effective forms of therapy for this socially crippling disease, but it also has profoundly influenced how we view the skin as a whole: the numerous competing theories on the pathogenesis of psoriasis published so far also are reflections on the evolution of mainstream thought in skin biology over the last decades. These days, conventional wisdom – infatuated with a T-cell-centered approach to inflammatory skin diseases – portrays psoriasis as an autoimmune disease, where misguided T lymphocyte activities cause secondary epithelial abnormalities. And yet, as this CONTROVERSIES feature reminds us, some authoritative “pockets of academic resistance” are still quite alive, and interpret psoriasis e.g. as a genetically determined, abnormal epithelial response pattern to infectious and/or physicochemical skin insults. Weighing the corresponding lines of argumentation is not only an intriguing, clinically relevant intellectual exercise, but also serves as a wonderful instrument for questioning our own views of the skin universe and its patterns of deviation from a state of homeostasis.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 119 (1988), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We investigated the in vivo effect of recombinant interferon-γ (IFN-γ) and tumour necrosis factor α (TNF-α) treatment of mice on the development of the delayed-type hypersensitivity (DTH) reaction and lichenoid tissue reaction (LTR) following the local injection of cloned autoreactive T cells. Both the DTH reaction and the LTR were significantly enhanced by pre-treatment with IFN-γ, but not with TNF-ã. Induction of class II MHC antigens on keratinocytes was not essential for the enhancement by IFN-γ. Administration of anti-IFN-γ antibody reduced the DTH reaction and LTR, although complete inhibition was not observed with our treatment regimen. The ability of IFN-γ to increase the number of the cloned T cells invading the epidermis in vivo, is in keeping with our previous observation that IFN-γ treatment of cultured keratinocytes markedly increased the adherence reaction between T cells and keratinocytes in vitro.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 112 (1985), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-069X
    Keywords: Adherence ; PMN ; Endothelial cells ; LTB4
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Adherence of polymorphonuclear leukocytes (PMNs) to endothelial cells (ECs) is a crucial step in the diapedesis of inflammatory cells to the site of inflammation. We have demonstrated that leukotriene B4 (LTB4), a metabolite of the arachidonic acid cascade, and N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) significantly enhance the binding of human PMNs to selected populations of human dermal microvascular endothelial cells (MECs) in vitro. MECs were isolated from the vascular-rich portion of foreskins of newborns. MECs were grown in Iscove's modified Dulbecco's media with 2% prepartum serum and 8% newborn calf serum on 1% gelatin-coated plastic dishes. PMNs isolated from five human donors were added to the culture dishes for varying time intervals (usually 30 min) in the presence and absence of the chemotactic stimuli LTB4 and FMLP. Addition of PMNs to MECs in the absence of chemotactic stimuli results in “baseline” binding to the MEC monolayer. About one in every 150 ECs binds more than five PMNs. These selected ECs are randomly distributed throughout the monolayer. LTB4 from 10-10 to 10-7 M increases the number of MECs which selectively bind PMNs by 260% at 10-7 M. FMLP also increases adherence in qualitatively and quantitatively similar fashion. These data support a role for LTB4 in the mediation of adherence of neutrophils to dermal MECs. In contrast to other endothelial cells from the large blood vessels, such as from umbilical veins or calf thoracic aortae, PMNs bind only to selected MECs in culture, even when stimulated with LTB4 or FMLP. These findings suggest a specific subpopulation of MECs which can be induced to express specific finding sites by LTB4.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-069X
    Keywords: Gamma interferon ; Keratinocytes ; Endothelial cells ; Adherence reactions ; T-cell subsets
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recombinant gamma interferon (r-IFN-γ) increases the adherence of peripheral blood mononuclear leukocytes (PBMLs) to cultured keratinocytes and cutaneous microvascular endothelial cells (MECs). To determine which specific type of PBMLs bound to these r-IFN-γ treated cells, we performed immunophenotyping on the adherent PBMLs. The adherent PBMLs were detached from the r-IFN-γ treated keratinocytes and MECs by adding EDTA, and collected by cytocentrifugation, followed by immunocytochemical staining using a panel of monoclonal antibodies. Our results reveal that the relative adherent population of PBMLs was composed of approximately 60%–70% monocytes and 18%–24% Leu 2+T lymphocytes (T-cytotoxic/suppressor) which preferentially bound to r-IFN-γ treated keratinocytes and MECs. There was some lesser binding by Leu 3+ lymphocytes (T-helper/inducer); approximately 8%, and no binding of B lymphocytes. Since r-IFN-γ also induced HLA-DR expression in keratinocytes and MECs, these in vitro data suggest that r-IFN-γ may play an important role in the immunobiology of diverse skin diseases such as graft vs host disease, lichen planus, and other inflammatory dermatoses, because the keratinocytes express HLA-DR and the predominant T-cell subset in the epidermis is Leu 2+ (over the Leu 3+T cell) in all of these conditions. These results represent a direct attempt to explain in situ immunophenotypic mononuclear leukocyte subset distribution patterns by using r-IFN-γ and purified cultured cells such as keratinocytes and MECs. We propose that IFN-γ, by both increasing the adherence of PBMLs, and promoting selective binding of monocytes and Leu 2+T lymphocytes to both keratinocytes and MECs, may be important in regulating PBML localization and recirculation in the skin.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 280 (1988), S. 279-281 
    ISSN: 1432-069X
    Keywords: Substance P ; Neuropeptides ; PBML ; T cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The release of neuropeptides, such as substance P (SP) and somatostatin (SOM), from primary sensory nerve fibers has been implicated in the modulation of local immune responses in surface tissues, such as the skin, the pulmonary airways, and the gastrointestinal mucosa. We have investigated the influence of six neuropeptides substance P (SP), somatostatin (SOM), substance K (SK), vasoactive intestinal peptide (VIP), bombesin (BOM), and adrenocorticotropic hormone (ACTH) on the proliferation of resting and partially stimulated human peripheral blood mononuclear leukocytes (PBMLs) and T lymphocytes. Neuropeptides in concentrations from 10-7 to 10-12 M were added to either resting or partially stimulated cells [interleukin-2 (IL-2), concanavalin A (Con A), and phytohemagglutinin (PHA)]. Cellular proliferation was assessed by incorporation of 3H-thymidine after 72h. With the exception of SP, no significant effect of any of these neuropeptides on 3H-thymidine incorporation was found. In resting cells, 10-9 MSP elicits an 80... maximal increase of 3H-thymidine incorporation, whereas no statistically significant effect on partially stimulated leukocytes was found. These results contradict a previous report on a significant mitogenic effect of SP on partially stimulated T cells. Considering the very minimal effect of SP on resting cells and, particularly, the absence of an effect on partially stimulated cells, we would question a significant modulatory role for SP and the five other neuropeptides in the proliferation of immunocompetent cells in skin.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-069X
    Keywords: ICAM-1 ; Keratinocytes ; LPS ; TNF-α ; Dendritic cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 284 (1992), S. S10 
    ISSN: 1432-069X
    Keywords: Psoriasis ; Cytokines ; Adhesion molecules ; Chemotaxins ; Keratinocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary For the better part of the past century, dermatologists have regarded the skin primarily as a large protective coat. Epidermal keratinocytes were highlighted for their production of keratins and lipids, which contributed to the structural integrity and barrier formation of skin. This “saran-wrap” perspective of skin mentioned keratinocytes only in cutaneous inflammatory reactions as passive targets for damaging diffusion products of infiltrating leukocytes. However, sufficient compelling in vitro and in vivo evidence is rapidly accumulating to support the novel perspective that epidermal keratinocytes can initiate and actively participate in the perperuation of numerous cutaneous inflammatory reactions that involve a highly diverse array of inciting agents. This presentation emphasizes the keratinocyte and highlights the dynamic immunomodulatory capacity of this overlooked epidermal cell.
    Type of Medium: Electronic Resource
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