Acidification in the epidermis and the role of secretory phospholipases

Abstract

The function of the epidermis is to form an effective barrier between the dry, external environment and the interior of the body. The barrier specifically resides in the extracellular lipid membranes of the stratum corneum (SC) and an acidic pH is necessary to maintain its competency against various insults. The purpose of this review is to explore the mechanisms which are postulated to contribute to the acidification of the stratum corneum, including both exogenous and endogenous sources. However, recent research as pointed to several endogenous mechanisms as the major source of acidification, including a sodium/proton pump (NHE1) and free fatty acid conversion from phospholipids by secretory phospholipase A2 (sPLA2). sPLA2 has been shown to play a central role in the formation of the SC “acid mantle” in the early maturation of the epidermis postnatally. Many aspects of this enzyme family are complex and still being elucidated in research and the most recent findings on the localization and functions of sPL A2-IB, -IIA, -IIC, -IID, -IIE, -IIF, -III, -V, -X and -XII in the epidermis are presented here. Given their role in inflammatory dermatoses, such as psoriasis and atopic dermatitis, understanding this complex enzyme family can lead to novel, life-changing therapies.

Pyrrolidone carboxylic acid levels or caspase-14 expression in the corneocytes of lesional skin correlates with clinical severity, skin barrier function and lesional inflammation in atopic dermatitis

“…Skin surface pH is influenced by SC acidification [36] originated from free fatty acids generated by secretory phospholipase 2 (sPLA2), tUCA and PCA generated by filaggrin degradation, and hydrogen ions (H + ) by the sodium/ hydrogen antiporter (NHE1) [37]. However, the interplay and impact of each individual source on the formation of the acidic skin surface remain unclear [38].…”

Do Repeated Skin Barrier Measurements Influence Each Other's Results? An Explorative Study

“…These changes rather entail an increased susceptibility towards external barrier perturbations and delayed barrier recovery [31,32] than representing actually existent skin disorders in elderly individuals. The effect of increased skin surface pH is clinically expressed as a propensity towards cutaneous infections and vulnerability of the skin barrier permeability homeostasis, as an extensive role in these mechanisms is attributed to the skin surface acidity [33,34,35]. On the other hand, the decreased TEWL rates found in chronologically aged skin are regarded to be of multifactorial origin.…”

Consistency of the Proteome in Primary Human Keratinocytes With Respect to Gender, Age, and Skin Localization

“…Keratinocytes account for 95% of all cells of the epidermis and hence are of high interest for studying epidermis functions. They are employed, among others, in research on epidermis acidification (2), DNA degradation in skin (3), local immune response in the skin (4), fatty acid transport and metabolism (5), cell-regeneration (6), and differentiation (7)(8)(9)(10), on the role of stem cells in tissue homeostasis and tumor formation (11), as well as integrin functions (12,13) and celladhesion (14). However, the short keratinocyte life cycle of about 4 weeks requires a steady supply of fresh tissue samples, and a concern is that varying constitutional factors such as age, gender, and anatomic site may compromise experimental results.…”