R C Kiekens

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (11)59.02 Total impact

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    ABSTRACT: UV-induced skin damage is the result of a complex cascade of events. Many studies have focused on the skin effects induced by UV-B or UV-A separately. Recently a UV-source that emits UV-B and UV-A together in a ratio comparable to daily sunlight has been introduced: i.e. solar simulated radiation (SSR). By exposing human skin type I-III to erythematogenic doses of UV (> or =1 MED) emitted by a SSR source we have noticed that: (a) neutrophils are initially the main infiltrating cell type in the dermis and (b) these infiltrating cells are the a key source of in vivo enzymatically [corrected] active enzymes such as elastase, [corrected] matrix metallo proteinases-1 and -9 (MMPs-1 and -9). These enzymes are relevant to the process of photoaging, as they break down the extracellular matrix. Keratinocytes and fibroblasts also produce matrix degrading enzymes, but to a lesser extent. Our results indicate a primary role for infiltrating neutrophils in the initial steps of photoaging. This is further supported by the observation that after exposure of skin type VI to physical doses of SSR, equivalent to those used for skin types I-III, no neutrophils and neutrophil-derived enzymatic activity were observed, explaining why skin type VI is [corrected] less susceptible to photoaging than skin types [corrected] I-III. Statement: Although most of the data, referred to, have been published, the current perspective in which they are put together is completely novel and has not been published elsewhere.
    Photochemical and Photobiological Sciences 02/2006; 5(2):184-9. · 2.92 Impact Factor
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    F Rijken, R C M Kiekens, P L B Bruijnzeel
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    ABSTRACT: The pathophysiology of photoageing of the skin has been studied extensively. Matrix metalloproteinases (MMPs) originating from keratinocytes and fibroblasts are thought to play a primary role in this process. Although neutrophils are potent producers of a wide array of proteolytic substances and are present in sunburned skin, their contribution to the pathophysiology of photoageing has been described only in murine studies. To determine the role of neutrophils in photoageing of human skin. Healthy white-skinned volunteers were recruited and their sun-protected buttock skin was exposed to solar-simulated radiation (SSR) in dose-response and time-course studies. Punch biopsies were taken and the influx of neutrophils and the expression of neutrophil elastase and MMPs was studied using immunohistochemical techniques and in situ zymography. Neutrophil elastase and MMPs were detected only in skin irradiated with erythemogenic doses (> or = 1 minimal erythema doses) of SSR. Immunohistochemical double staining demonstrated neutrophils to be the major source of MMP-1, MMP-8 and MMP-9. In situ zymography showed elastase, collagenase and gelatinase enzyme activity in those cells. Our study suggests that neutrophils participate in the process of photoageing of human skin as they infiltrate the skin and release enzymatically active elastase (neutrophil elastase), collagenase (MMP-1) and gelatinase (MMP-9).
    British Journal of Dermatology 03/2005; 152(2):321-8. · 3.76 Impact Factor
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    ABSTRACT: Black skin is more resistant to the deleterious effects of ultraviolet radiation than white skin. A higher melanin content and a different melanosomal dispersion pattern in the epidermis are thought to be responsible for this. Our purpose was to compare skin responses in black and white skin following exposure to solar-simulating radiation (SSR) to further investigate the photoprotective properties of black skin. Six volunteers of skin phototype I-III (white) were exposed to (doses measured directly with a Waldmann UV detector device) 12,000-18,000 mJ per cm2 (2 MED) of SSR and compared with six volunteers of skin phototype VI (black) exposed to 18,000 mJ per cm2 (<1 MED) of SSR. The presence and distribution of skin pigment, DNA photodamage, infiltrating neutrophils, photoaging associated proteolytic enzymes, keratinocyte activation, and the source of interleukin 10 (IL-10) in skin biopsies taken before and after exposure were studied. In all white skinned subjects, 12,000-18,000 mJ per cm2 of SSR induced DNA damage in epidermal and dermal cells, an influx of neutrophils, active proteolytic enzymes, and diffuse keratinocyte activation. Additionally, in three of the white skinned volunteers IL-10 positive neutrophils were found to infiltrate the epidermis. Except for DNA damage in the supra basal epidermis, none of these changes was found in black skinned subjects. Increased skin pigmentation appears to be primarily responsible for the observed differences in skin responses. Our data could provide an explanation as to why black skin is less susceptible to sunburn, photoaging, and skin carcinogenesis.
    Journal of Investigative Dermatology 06/2004; 122(6):1448-55. · 6.19 Impact Factor
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    ABSTRACT: Macrophages and dendritic cells may play a role in chronicity of atopic dermatitis (AD); however, so far only limited data are documented on the distribution of these cells in the skin during cutaneous inflammation. To gain better insight into the presence and distribution of macrophage and dendritic cell (sub)populations in acutely and chronically inflamed skin of AD patients. Chronic inflammatory reactions were studied in lesional AD skin biopsies; the atopy patch test was used as a model for the initiation of AD lesions, representing acute inflammation. To determine the number and phenotype of different dermal macrophage and dendritic cell populations immunohistochemistry and digital imaging were used. There was an increase in macrophage numbers in acutely and chronically inflamed AD skin, whereas absolute dendritic cell numbers were unchanged, compared with non-lesional AD skin. Furthermore, phenotypically heterogeneous and overlapping macrophage and dendritic cell populations were present in inflamed AD skin. The classic macrophage marker CD68 and prototypic dendritic cell marker CD1a could bind to the same cell subpopulation in the dermis of inflamed AD skin. Mannose receptors were expressed mainly by macrophages in inflamed AD skin. In this study we observed changes in macrophage number and phenotype during cutaneous inflammation in AD. Dendritic cell numbers did not change; however, phenotypically dendritic cell and macrophage subpopulations showed increasing overlap during inflammation in AD skin. We show for the first time that within tissue-specific macrophage populations further subpopulations are present, and that monocyte-derived cells may express markers for both dendritic cells and macrophages. Our results point to the existence of a heterogeneous pool of macrophage/dendritic cell-like cells, from which subpopulations of dermal macrophages and dendritic cells arise.
    British Journal of Dermatology 01/2002; 145(6):957-65. · 3.76 Impact Factor
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    ABSTRACT: Atopic dermatitis is an allergic skin disease characterized by elevated total and antigen-specific serum IgE and IgG4 levels. In acute and chronic cutaneous inflammation, large cellular infiltrates including T cells, dendritic cells and macrophages are found, especially in the dermis. These cells play an important part in the regulation of local inflammatory reactions. Receptors binding IgG (FcgammaR) are involved in dendritic cell and macrophage function. In this study, we examined the in vivo distribution and cellular expression of the three classes of leucocyte FcgammaR in human skin during acute and chronic cutaneous inflammation in atopic dermatitis. Atopy patch test skin was used as a model for acute inflammation in atopic dermatitis, while chronic lesional skin was used to investigate FcgammaR expression in chronically inflamed skin. In atopy patch test sites no increase in the number of CD1a+ dendritic cells and a slight increase in macrophages compared with non-lesional skin was observed. Our results showed increased expression of FcgammaRI (CD64) and FcgammaRIII (CD16) in acutely inflamed skin as well as in chronically inflamed lesional skin, compared with healthy and non-lesional atopic dermatitis skin. FcgammaRI was expressed by RFD1+, RFD7+ and CD68+, but not by CD1a+ dermal dendritic cells. RFD1+ dendritic cells and CD68+ macrophages were the main FcgammaRIII-expressing cells during the acute inflammatory reaction. The significant increase in expression of FcgammaRIII (CD16) and FcgammaRI (CD64) probably results from upregulation of the receptors on resident cells. Insight into the presence of FcgammaR+ cells in human skin during inflammation is important both for our understanding of skin immune reactions and the development of new therapeutic concepts.
    British Journal of Dermatology 07/2000; 142(6):1106-13. · 3.76 Impact Factor
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    ABSTRACT: We constructed an immunotoxin, composed of an antibody directed against the high-affinity IgG receptor CD64 and Ricin-A, with the aim of resolving chronic inflammation through elimination of activated macrophages. In vitro, this immunotoxin proved very efficient in inducing apoptosis in activated macrophages, leaving resting and low CD64-expressing macrophages unaffected. We examined the activity of our immunotoxin in a sodium lauryl sulfate (SLS)-induced cutaneous inflammation model, using transgenic mice expressing human CD64. Upon intradermal injection of the immunotoxin (IT), cutaneous inflammation resolved in 24 h. This was demonstrated histologically by clearance of all CD64-expressing macrophages, followed by clearance of other inflammatory cells. Clinical parameters associated with inflammation, such as local skin temperature and vasodilation, also decreased.
    Nature Biotechnology 02/2000; 18(1):48-51. · 32.44 Impact Factor
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    ABSTRACT: After ultraviolet exposure Langerhans cells (epidermal CD1a+ cells) disappear from the healthy skin, and CD11b+ macrophage-like cells, which are reported to produce interleukin-10, appear in a matter of days. These phenomena are related to the ultraviolet-induced local suppression of contact hypersensitivity reactions. A defect in this suppression might allow inadvertent immune reactions to develop after ultraviolet (over)exposure; i.e., it could cause ultraviolet-B-induced polymorphous light eruption. In order to test this we first exposed buttock skin of eight healthy volunteers to six minimal erythema doses from Philips TL12 lamps, and indeed observed a dramatic disappearance of CD1a+ cells 48 and 72 h later, at which time the number of CD11b+ cells increased in the dermis, and some occurred in the epidermis. The epidermis thickened and showed large defects, filled by CD11b+ cells, just below the stratum corneum. In 10 patients with polymorphous light eruption (five with a normal minimal erythema dose and five with a low minimal erythema dose) CD1a+ cells were present in the epidermis as well as in the dermis before exposure. Strikingly, these cells were still present in considerable number at 48 and 72 h after exposure to six minimal erythema doses. CD11b+ cells already present in the dermis before ultraviolet exposure, increased after ultraviolet exposure, and subsequently also invaded the epidermis. Despite the six minimal erythema doses, there were no apparent defects in the epidermis of the polymorphous light eruption patients. This deviant early response to ultraviolet radiation is likely to be of direct relevance to the polymorphous light eruption and is perhaps useful as a diagnostic criterion.
    Journal of Investigative Dermatology 08/1999; 113(1):4-10. · 6.19 Impact Factor
  • Journal of Dermatological Science - J DERMATOLOGICAL SCI. 01/1998; 16.
  • Immunology Letters. 56:247.