Ultraviolet B radiation generates platelet-activating factor-like phospholipids underlying cutaneous damage

Ultraviolet B light ( UVB) causes cutaneous inflammation and cell death, but the agents responsible are not defined. These studies examined the role of the platelet- activating factor ( PAF) signaling system in UVB- mediated effects. Expression of the PAF receptor in the PAF receptor- negative epidermoid cell line KB augmented apoptosis in response to UVB irradiation. Overexpression of the PAF receptor in primary human keratinocytes also enhanced UVB- mediated apoptosis in vitro, and it enhanced apoptosis in an in vivo model of human keratinocytes grafted onto severe combined immune- deficient ( SCID) mice. To define the mechanism by which UVB activates the PAF receptor, we used mass spectrometry to demonstrate significant amounts of the C-4 PAF analogs 1- alkyl- 2( butanoyl and butenoyl)- sn- glycero- 3- phosphocholine, as well as native PAF in an epidermal cell line after UVB irradiation. Supplementing the cells with the precursor phospholipid 1- hexadecyl- 2-arachidonoyl- sn- glycero- 3- phosphocholine ( HAPC) increased the amount of C-4 PAF analogs recovered after UVB exposure. We irradiated HAPC directly and found, even in the absence of a photosensitizer, fragmentation to C-4- PAF receptor ligands. We conclude UVB photo- oxidizes cellular phospholipids, creating PAF analogs that stimulate the PAF receptor to induce further PAF synthesis and apoptosis. PAF signaling may participate in the cutaneous inflammation that occurs during photo- aggravated dermatoses.