Piet E.J. van Erp

In Vivo Induction of Cutaneous Inflammation Results in the Accumulation of Extracellular Trap-Forming Neutrophils Expressing RORγt and IL-17

Clinical trials successfully using antibodies targeting IL-17 in psoriasis support the importance of IL-17 in the pathophysiology of this disease. However, there is a debate concerning the source and dynamics of IL-17 production in inflamed skin. Here we characterized IL-17-producing immune cells over time, using two established in vivo models of human skin inflammation that share many histological features with psoriasis, i.e., leukotriene B4 application and tape-stripping. Both treatments revealed a clear influx of neutrophils and T cells. Staining for IL-17 revealed that the majority of IL-17 was expressed by neutrophils and mast cells, in both models. Neutrophils, but not mast cells, coexpressed the IL-17-associated transcription factor RORγt and were able to form extracellular traps. While the presence of mast cells remained steady during the skin inflammatory process, the presence of neutrophils was clearly dynamic in time. Therefore, it is attractive to hypothesize that IL-17+/RORγt+ neutrophils contribute to human skin inflammation in vivo and possibly to the pathogenesis of skin diseases such as psoriasis. Surprisingly, T cells represented a minority of the IL-17-expressing cell population. These observations challenge the classical opinion that IL-17 is predominantly associated with T cells in skin inflammation.

Studies on the plasma membrane of normal and psoriatic keratinocytes

A method is described for the preparation of isolated keratinocytes suitable for subsequent biochemical studies. Scanning electron microscopy showed that the maturation process is accompanied by an increase in cell size and a shortening and eventual loss of microvilli. Psoriatic keratinocytes are distinguishable by exhibiting longer microvilli at all levels of maturation.

Topical treatment of psoriatic plaques with 1,25‐dihydroxyvitamin D3: a cell biological study

Calcitriol, 1α,25 dihydroxycholecalciferol (α.25 (OH)2 D2) is a natural active vitamin D3 metabolite, which has been shown to have antipsoriatic efficacy. In vitro studies have demonstrated that calcitriol influences various aspects of inflammation, epidermal proliferation and keratinization. The aim of the present study was to determine to what extent caicitriol (3 μ/g in white petrolatum) affects these parameters in vivo.

Calmodulin levels are grossly elevated in the psoriatic lesion.

Levels of the intracellular calcium receptor, calmodulin, in the psoriatic lesion are more than thirty times higher than normal. By contrast, values in the clinically uninvolved psoriatic skin are unchanged.

Markers for proliferation and keratinization in the margin of the active psoriatic lesion.

To study the development of the psoriatic lesion, biopsies were taken from the margin of spreading plaques and acute pinpoint papules. Consecutive sections across the margin were stained using different monoclonal antibodies to characterize epidermal growth (Ki‐67) and abnormal keratinization (Ks8.12, RKSE60). All three immunohistochemical markers showed pronounced changes in the lesional skin with a clear transition to the uninvolved skin. The suprabasal Ks8.12 binding was the earliest change found in the epidermis, and its localization high in the suprabasal compartment indicates that metabolic dysregulation in this cell population was not a consequence of the recruitment process in the basal layer.

Confirmation of raised phospholipase A2 activity in the uninvolved skin of psoriasis

Phospholipase A2 has been measured in the lesions and the ‘uninvolved’ skin of patiens with psoriasis. We confirm a previous report that there is a generalized increase in the activity of this enzyme in psoriatic skin.

Studies on the plasma membrane of normal and psoriatic keratinocytes. 5. Lectin binding

The glycocalyx of epidermal keratinocytes from psoriatic patients has been investigated by means of lectins. Striking changes were found in the levels of glucose and/or mannose (concanavalin A) and of N‐acetylglucosamine and/or sialic acid (wheat germ agglutinin) on the surface of cells from the psoriatic lesion. Smaller but significant changes were seen in the clinically uninvolved epidermis of the patient. A marked increase in the affinity of the cell surface for Ulex europus agglutinin (fucose‐specific) confirms our previous reports of structural alterations in fucose‐containing oligosaccharides in psoriasis.

Studies on the plasma membrane of normal and psoriatic keratinocytes. 4. Characterization of glycoconjugates

A substantial proportion (20–50%) of radioactive sugar incorporated into glycoconjugates by normal human keratinocytes was soluble in chloroform‐methanol; using (14C)‐galactose as precursor about half of this fraction was neutral lipid. The incorporation of labelled sugars into the lipid fraction was consistently increased in keratinocytes derived from psoriatic lesions.

Studies on the plasma membrane of normal and psoriatic keratinocytes. 3. Uptake of labelled sugars and their incorporation into glycoconjugates

We report the uptake of four labelled sugars by keratinocytes isolated from normal epidermis, psoriatic ‘uninvolved’ skin and psoriatic lesions. Our findings include the following:

Understanding the Acute Skin Injury Mechanism Caused by Player-Surface Contact During Soccer: A Survey and Systematic Review.

Background: Superficial skin injuries are considered minor, and their incidence is probably underestimated. Insight into the incidence and mechanism of acute skin injury can be helpful in developing suitable preventive measures and safer playing surfaces for soccer and other field sports. Purpose: To gain insight into the incidence and severity of skin injuries related to soccer and to describe the skin injury mechanism due to player-surface contact. Study Design: Systematic review; Level of evidence, 4. Methods: The prevention model by van Mechelen et al (1992) combined with the injury causation model of Bahr and Krosshaug (2005) were used as a framework for the survey to describe the skin injury incidence and mechanism caused by player-surface contact. Results: The reviewed literature showed that common injury reporting methods are mainly based on time lost from participation or the need for medical attention. Because skin abrasions seldom lead to absence or medical attention, they are often not reported. When reported, the incidence of abrasion/laceration injuries varies from 0.8 to 6.1 injuries per 1000 player-hours. Wound assessment techniques such as the Skin Damage Area and Severity Index can be a valuable tool to obtain a more accurate estimation of the incidence and severity of acute skin injuries. Conclusion: The use of protective equipment, a skin lubricant, or wet surface conditions has a positive effect on preventing abrasion-type injuries from artificial turf surfaces. The literature also shows that essential biomechanical information of the sliding event is lacking, such as how energy is transferred to the area of contact. From a clinical and histological perspective, there are strong indications that a sliding-induced skin lesion is caused by mechanical rather than thermal injury to the skin.