STRUCTURAL AND BIOCHEMICAL BASIS FOR THE UVB-INDUCED ALTERATIONS IN EPIDERMAL BARRIER FUNCTION

Ultraviolet light (UVR) induces a myriad of cutaneous changes, includi ng delayed disruption of the permeability barrier with higher doses. T o investigate the basis for the WE-induced barrier alteration, we asse ssed the epidermal lamellar body secretory system at various time poin ts before and after barrier disruption with a single high dose of UVB (7.5 MED) to murine epidermis. Morphological data were correlated with changes in epidermal proliferation and lipid synthesis, indicative of lamellar body generation. Twenty-four hours following UVB, the stratu m corneum (SC) is normal, but a layer of abnormal, vacuolated, and lam ellar body (LB)-deficient cells is present, immediately beneath the st ratum granulosum (SG)ISC interface. Immediately subjacent to this band of damaged cells, normal keratinocytes that contain intact LBs are pr esent. By 72 h, concomitant with the appearance of a barrier abnormali ty, extensively damaged cells persist at the SC/SG interface, and abno rmal lamellar membrane structures appear in the lower SC. Upper stratu m spinosum (SS) and lower SG cells appear normal, with increased numbe rs of LBs. A barrier abnormality is still present at 96 h, in associat ion with membrane abnormarities in the lower SC interstices, but up to four normal-appearing, subjacent SG cell layers are present. By 120 h , accelerated LB formation and precocious LB extrusion occur throughou t the thickened SG; normal lamellar membranes are present in the lower SC; and barrier recovery is almost complete. Whereas, epidermal synth esis of the major barrier lipid species (i.e., cholesterol, fatty acid s, and ceramides, including acylceramides) is reduced or unchanged at 24 and 48 h, it increases significantly 72 h after exposure to UVB. Th erefore, the delayed disruption of the permeability barrier following acute UVB exposure results from the arrival of a band of lamellar body -incompetent (i.e., damaged) cells at the SG/SC interface. The subsequ ent, rapid recovery of the barrier, in turn, results from compensatory hyperplasia of subjacent, undamaged SS/SG cells, generating increased numbers and contents of LB. These results underscore the critical rol e of the stratum compactum in mediating barrier function, and suggest that beneficial therapeutic effects of UV exposure may be due to enhan ced lipid production and barrier regeneration.