1. ^*Dermatology and Medical Service, Veterans Affairs Medical Center, San Francisco, California, USA
2. ^†Departments of Dermatology and Medicine, University of California, San Francisco, California, USA
3. ^‡Department of Dermatology and Allergology, Friedrich-Schiller-University, Jena, Germany
4. ^§INSERM U.346/CNRS, Human Skin and Immunity, E. Herriot Hospital, Lyon, France
5. ^¶UMR 5165 CNRS, Université Toulouse III, France

Correspondence: Joachim W. Fluhr, MD, Dermatology Service (190), Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, California 94121, USA. Email: fluhr@derma.uni-jena.de

Received 22 December 2003; Revised 12 February 2004; Accepted 15 February 2004; Published online 30 June 2003.

Abstract

At birth, neonatal stratum corneum (SC) pH is close to neutral but acidifies with maturation, which can be ascribed, in part, to secretory phospholipase A₂ and sodium/hydrogen antiporter 1 (NHE1) activities. Here we assessed the functional consequences of a neutral SC pH in a newborn rat model. While basal transepidermal water loss rates are near normal, barrier recovery (BR) rates after acute barrier disruption were delayed in newborn animals. The abnormality in barrier homeostasis could be improved by topical applications of an acidic buffer, indicating that barrier abnormality is primarily due to high SC pH. The delay in BR correlated with incompletely processed lamellar membranes and decreased activity of beta-glucocerebrosidase. Inhibition of NHE1 delayed BR after acute barrier perturbation. SC integrity was abnormal in newborn animals. Electron microscopy demonstrated decreased corneodesmosomes (CD) in newborn animals with decreased expression of desmoglein 1 and corneodesmosin. Serine protease activation appears to be responsible for CD degradation in newborn animals, because serine protease activity is increased in the SC and it can be reduced by acidification of the SC. The delay in acidification of neonatal SC results in abnormalities in permeability barrier homeostasis and SC integrity and are likely due to pH-induced modulations in enzyme activity.