ABNORMAL EXPRESSION OF SPHINGOMYELIN ACYLASE IN ATOPIC-DERMATITIS - AN ETIOLOGIC FACTOR FOR CERAMIDE DEFICIENCY

Previously, we demonstrated that there is a marked reduction in the am ount of ceramide in the stratum corneum of both lesional and nonlesion al forearms in atopic dermatitis (AD), suggesting that an insufficienc y of ceramides in the stratum corneum is an etiologic factor in atopic dry and barrier-disrupted skin, In this study, we investigated, as a possible mechanism involved in the ceramide deficiency, whether sphing omyelin (SM) metabolism is altered in AD as compared to normal control s, In stripped stratum corneum and biopsied whole epidermis of patient s with AD, SM hydrolysis as measured at pH 4.7 using [choline-methyl-C -14]sphingomyelin as a substrate were markedly increased by 27- and 7- fold, respectively, Radio-thin-layer chromatography of the reaction pr oducts revealed that, whereas the SM hydrolysis in age-matched normal controls were associated with sphingomyelinase (SMase) that degrades S M to yield ceramides and phosphorylcholine (PC), most of the SM hydrol ysis detected in AD were attributable not to the SMase but to a hither to undiscovered epidermal enzyme, SM acylase, which releases free fatt y acid and sphingosyl-PC (Sph-PC) instead of ceramides, The potential of this acylase-like enzyme to generate Sph-PC through SM hydrolysis w as corroborated by thin-layer chromatographic analysis of the reaction products obtained using porcine kidney acylase, followed by high-perf ormance liquid chromatography-mass spectrometry, Furthermore, Sph-PC w as also detected by high-performance liquid chromatography-mass spectr ometry after incubation of SM with atopic stratum corneum samples, On the other hand, the stratum corneum of patients with contact dermatiti s or chronic eczema exhibited neither increased SM hydrolysis nor the generation of Sph-PC upon radio-thin-layer chromatographic analysis, T hese findings suggest that SM metabolism is altered in AD, resulting i n a decrease in levels of ceramides, which could be an etiologic facto r in the continuous generation of atopic dry and barrier disrupted ski n observed in AD.