Читать книгу pH of the Skin: Issues and Challenges - Группа авторов - Страница 56

A crucial element in the skin adaptation is the maturation of the acid mantel of the epidermis of newborns. It is widely recognized that the surface pH of human adult skin is acidic with a pH between 5 and 5.5 [7, 8]. Yet, the skin surface of term newborns is not fully acidified and shows elevated pH values compared to that of adults [8, 9], which can predispose to the development of dermatoses in infancy such as the diaper dermatitis [7, 8]. Different mechanisms are responsible for the formation of an acidic skin surface pH. These include endogenous pathways – free fatty acid generation from phospholipid hydrolysis [10–12], the sodium/proton pump antiporter, sodium/hydrogen antiporter-1 [10, 13, 14] and the generation of acidic metabolites of filaggrin metabolism, such as cis-urocanic acid from histidine [15, 16]. However, the last pathway is still under discussion [17] (Fig. 2). In addition, exogenous mechanisms, such as the eccrine gland-derived lactic acid [18, 19] and the free fatty acids of pilosebaceous origin [20, 21], are likely to contribute to the skin surface acidification even though the sebaceous gland activity is low at birth. None of these potential mechanisms has been linked to the pH formation in human newborns so far [22, 23].

The acidic pH of SC is essential for the formation of intact skin barrier functions. Although basal permeability barrier function is competent at birth [13], skin surface pH is close to neutral at birth both in humans and in different animal models [6, 24, 25]. Following acute barrier disruption by either tape stripping or acetone treatment, barrier recovery was markedly delayed in a newborn rat model [24]. Further animal studies excluded a variety of exogenous and endogenous mechanisms previously thought to be implicated in post-natal SC acidification [10]. These studies showed a central role for two endogenous mechanisms, the secretory phosholipase A2 pathway and sodium-proton exchanger, in the generation of the postnatal acid mantel. The functional consequences of neutral pH of SC included abnormal permeability homeostasis and defects in SC integrity, attributed respectively to the reduced beta glucocerebrosidase (β-Gluc Cer’ase) and increased serine proteases activity directly after birth [24]. Exogenous acidification of the SC normalized barrier recovery kinetics and improved SC integrity [24].

SC acidity is essential for the epidermal barrier homeostasis (barrier recovery after acute barrier insult), the latter being delayed at a neutral or elevated pH, due to disturbance in processing secreted extracellular SC lipids, while lipid secretion remains unimpaired [26]. Furthermore, disturbance of lipid processing enzymes has been shown in neonatal skin [26]. The impairment of the barrier homeostasis was attributed to the acidic pH optima of the key lipid-processing enzymes in the upper part of the SC, that is, β-Gluc-Cer’ase and acidic sphingomyelinase. Increases in the pH resulted in perturbations of lipid processing and in an impairment of barrier homeostasis. In subsequent studies, it was shown that prolonged increase of pH leads to the degradation of these enzymes by sustained serine proteases activity [27]. Prolonged increase of pH not only delays barrier recovery but also increases basal transepidermal water loss [27]. It has been proposed that an acidic pH directly impacts lipid-lipid interactions in the SC extracellular lamellar bilayers [28].