Effects of retinoid (Ro 10-9359) on the plasma membrane of keratinocytes in patients with psoriasis: A freeze-fracture analysis

Abstract

Although many thin-section ultrastructural studies have recently been carried out on the effects of retinoids on psoriatic skin, few freeze-fracture studies have been performed. Since keratinocyte membrane disturbances may be involved in psoriasis and since retinoids biochemically affect biologic membranes, we employed a freeze-fracture technique to study the effects of retinoid on the junctional and internal structures of membranes. Lesional and nonlesional skin was biopsied from 5 patients with psoriasis vulgaris before and 3 of them after oral treatment with 50 mg of etretinate (Ro 10-9359) per day for 4 weeks. The most remarkable finding was the reduction in size of desmosomes - from 0.43 ± 0.07 μm to 0.23 ± 0.08 μm diameter in spinous cells and 0.35 ± 0.03 μm to 0.14 ± 0.03 μm in horny cells in lesional skin. Similar results were obtained in nonlesional skin. This reduction in desmosomal size appears to be large enough to produce an extensive exfoliation. It was also of great interest that the intramembranous particle density on the P face (the fracture face of the protoplasmic half-layer) of the spinous cell plasma membranes was 1140 ± 57/μm2 in lesional and 429 ± 89/μm2 in nonlesional skin before treatment, and 1184 ± 93/μm2 and 1179 ± 147/μm2 after treatment, respectively, although the lesions were clinically resolved. This may suggest that the agent does not revert the keratinocyte membrane from a psoriatic to a normal state despite clinical improvement. Many openings of pinocytotic (or exocytotic) vesicles were produced on the plasma membranes of keratinocytes. This was associated with the appearance of fine granular substances (so-called mucous-like substances) in the intercellular spaces.