UV Irradiation Induces Apoptosis of Keratinocytes and Clustering of Lupus Autoantigens in Apoptotic Surface Blebs

Because the epidermis is one of the physiologic targets of the immunopathologic response in lupus, several groups have established an in vitro epidermal model to address the fate of autoantigens in keratinocytes after irradiation with UVB (Casci-ola-Rosen et al. 1994, Furukawa et al. 1990,Golan et al. 1992,LeFeber et al. 1984,Natali and Tan 1973). One of the striking observations made was that several lupus autoantigens (including Ro/SSA, La/SSB, snRNP, and Sm) that are normally intracellular could be stained extracellularly in monolayers of human keratinocytes incubated for 20-24 hours after UV irradiation (Furukawa et al. 1990, Golan et al. 1992, LeFeber et al. 1984). Using a similar in vitro system, we demonstrated that keratinocytes become apoptotic within a few hours of irradiation (Casciola-Rosen et al. 1994). Further studies showed that the lupus autoantigens are strikingly redistributed in apoptotic cells, and they become clustered into two populations of structure at the surface of apop-totic cells: small blebs and apoptotic bodies (Fig. 17.1). Small surface blebs arise from fragmented rough endoplasmic reticulum and are highly enriched in Ro/SSA (52 kDa), ribosomal autoantigens, as well as those autoantigens found within the endoplasmic reticulum lumen (e.g., calreticulin). This marked enrichment in autoantigens in small surface blebs was accompanied by a concomitant depletion of these molecules from the cytosol. Apoptotic bodies contain nuclear autoantigens, which also undergo a striking redistribution and concentration during apoptosis. Thus,


Nucleosomes Ro (60 kDa) La Sm U1-70 kDa Ku/DNA-PK Mi-2 PARP NuMA

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