LAMELLAR BODY SECRETORY RESPONSE TO BARRIER DISRUPTION

Abundant evidence points to an important role for epidermal lamellar body secretion in permeability-barrier maintenance. However, the response of the lamellar body secretory system to barrier disruption has not been examined. Hence, we examined the lamellar body secretory response at various points after acetone-induced barrier abrogation in hairless mice in air-exposed animals and those occluded with impermeable versus vapor-permeable membranes. Tape-stripped animals served as a control for chemical toxicity. Barrier perturbation with either acetone or tape stripping was followed by rapid secretion of lamellar body contents from the uppermost granular cell layer, leaving the cytosol largely devoid of lamellar bodies. The newly secreted lamellar body contents comprised pleated sheets (not "discs," as previously thought), which unfurled in the intercellular spaces at the granular-cornified cell interface. At this time (15-30 min), the basic unit structure of the lamellar bilayers in the mid-to-upper stratum corneum appeared disorganized and interspersed with large lacunae, reflecting solvent extraction. Nascent lamellar bodies began to reappear in the granular cell cytosol by 30 min and by 360 min the cells displayed a full complement of normal-appearing lamellar bodies. Between 60 and 360 min, the density of lamellar body sheets at the granular-cornified cell interface increased, whereas the membrane bilayers of the outer stratum corneum remained disorganized. New lamellar bilayer units first appeared in the lower stratum corneum between 60 and 180 min, as a result of the transformation of secreted lamellar body sheets and over time these lamellae appeared at more apical locations. Occlusion with a water vapor-impermeable but not a vapor-permeable membrane resulted in a) decreased quantities of lamellar bodies and lamellar body-derived intercellular products; b) formation of lamellar bodies with abnormal internal contents; c) inhibition of lamellar body secretion; and d) inhibition of transformation of lamellar body-derived sheets into lamellar bilayer units. These results demonstrate the central role of the lamellar body-secretory system in barrier repair and homeostasis.