Aspects on the physiology of human skin: Studies using particle probe analysis

Abstract

The cellular part of the skin, the epidermis, is a very thin structure, approximately 120 μm thick, a fact which has hindered the exploration of the physiology of the epidermis in normal and pathological conditions. An additional complication is the fact that the epidermis contains layers of cells at different stages of differentiation. Therefore, conventional physiological capillary probes cannot, with any satisfactory precision, be located within a specified cell of a specified layer of the skin in vivo. Hence, alternative ways for the exploration of skin physiology have been sought for. In the past, analysis of the elemental content of skin was done as bulk measurements, and surprisingly wide ranges of elemental content were recorded. The width of these ranges was most certainly due to the sampling methods used rather than the sensitivity of the chosen method of analysis. Also, these older measurements did not discriminate between the different strata, and therefore the information provided little if any substance for a functional analysis of processes involved in normal and pathological differentiation of the epidermis. Particle probes, however, have been able to overcome such methodological problems. Over a period of 15 years we have studied normal human skin, normal‐looking, paralesional skin from psoriatics, and skin from persons suffering from atopic dermatitis using PIXE analysis. In recent years, trace elements have been shown to work as secondary messengers or regulatory substances. As an example, calcium (Ca2+) has proven to be a very important signalling substance in a great variety of cellular systems. Studies with the transmission electron microscope (TEM) as well as histochemical methods have allowed an understanding of the role of Ca2+ in the differentiation process of the epidermis. Ca2+ has also been shown to play an important role in apoptosis (programmed cell death), which is currently a hot subject for the obvious reason that the final differentiation step between the stratum granulosum level and the stratum corneum represents a particular aspect of programmed cell death. The importance of the balance between calcium and zinc in apoptosis has been clearly demonstrated in a number of cellular systems, but we have still to clarify the validity of topical treatment with Zn ointments in different skin conditions. Substantial iron (Fe) losses via psoriatic lesions were demonstrated more than two decades ago, and these data were given new meaning when we found that a more discrete loss occurs in clinically normal‐looking psoriatic skin. Obviously, such findings stress the importance of understanding the relation between the elemental content and normal and abnormal physiology. The ultimate goal of particle probe studies is to provide an understanding of the formation of a mature stratum corneum with a functional barrier reflected in physiological/biochemical mechanisms behind the properties of changed skin in patients afflicted with skin disorders of genetic or constitutional origin. This...

Evidence that TRPC1 contributes to calcium-induced differentiation of human keratinocytes

“…Keratinocytes cultured in low [Ca 2+ ] (e.g., 0.03 mM) show the proliferation phenotype but switch to a nonproliferative differentiation phenotype with expression of differentiation-related proteins including involucrin [4,12,24,36] when cultured in high [Ca 2+ ] (e.g., 1.2 mM). Transepithelial calcium gradients that are consistent with extracellular Ca 2+ induction of keratinocyte differentiation in vivo have been reported in situ [11,20]. The increase in external [Ca 2+ ] induces an increase in intracellular [Ca 2+ ] that is required for induction of keratinocyte differentiation [18].…”

Epidermal desquamation

“…Substantial amounts of a parenterally administered radioactive iron tracer were eliminated through epidermal desquamation in patients with exfoliative dermatitis [44]. Several groups have reported increased amount of iron in epidermis of psoriatic plaques compared to uninvolved epidermis or normal epidermis [48,49]. In contrast, another group found much less iron in psoriatic plaques than in normal skin [50].…”

Ras-independent Activation of the Raf/MEK/ERK Pathway upon Calcium-induced Differentiation of Keratinocytes

“…This is followed by increased expression of differentiation-associated proteins as well as induction of morphological changes characteristic of differentiation such as the establishment of intercellular desmosomal contacts (5,7). In addition to its well characterized effect on keratinocyte differentiation in vitro, calcium constitutes a gradient in epidermal layers (8,9), which also implies a function for calcium as regulator of keratinocyte growth and differentiation in vivo. Intracellularly, calcium has been shown to trigger phospholipase C␥ activation, thereby elevating cytosolic calcium levels (10,11).…”