Acidification in the epidermis and the role of secretory phospholipases

Epidermis forms a barrier between the dry external environment and the interior of the body, preventing water and ions from exiting, and toxins, antigens and bacteria from entering. Residing in the extracellular lipid membranes of the stratum corneum, this vital barrier requires an acidic environment in order to remain functional and competent against various insults. The acid pH not only limits the growth of pathogenic skin flora, but also is required for the enzymatic lipid processing that results in an effective permeability barrier. The mechanisms behind this "acid mantle" have long been debated. Originally, exogenous sources of acid were thought to cause this drop in SC pH. However, more recent evidence has emerged that identifies endogenous sources as the primary mode of SC acidification. A sodium/proton pump, NHE1, has been implicated in acidifying the border between stratum granulosum and SC. Another significant mechanism contributing to the acid mantle is free fatty acid conversion from phospholipid by a secretory phospholipase A2 (sPLA2). Lastly, urocanic acid generation via histidase is postulated to be another endogenous source of acid, although this has been disputed. Studies of the neonatal acidification processes in murine epidermis demonstrate the central role sPLA2 plays in forming the acid mantle at the beginning of life. Maintenance of an acidic SC in adults, however, appears to require additional mechanisms. This (secretory phospholipase A2 family) enzyme plays a significant and varied role in many mammalian cells, and the individual localization and function of the various sPLA2 members identified in skin (sPLA2-IB, -IIA, -IIC, -IID, -IIE, -IIF, -III, -V, -X, and -XII) still must be defined. More importantly, given the role of sPLA2s in inflammatory dermatoses such as atopic dermatitis and psoriasis, further discoveries could lead to novel, life-changing therapies.