These studies examining the transfer of UVB-mediated tolerance indicated that inhibition of both the serotonin and PAF-R systems were necessary to block the production of these B cells (Matsumura em et al /em ., 2006). These studies suggest that UVB irradiation results in epidermal production of PAF agonists, which then take action on PAF-R-positive bone marrow-derived cells to upregulate IL-10 through COX-2-generated prostaglandins. INTRODUCTION UVB radiation (290?320 nm; UVB) is the most important environmental carcinogen, and skin is the major target. Non-melanoma skin cancer is the most common type of cancer diagnosed, and UV radiation is the source (Kripke, 1977; Carroll short-chained acyl glycerophosphocholines (GPCs) with PAF-R agonistic activity can also be produced through free radical-mediated damage NCT-501 (Marathe (Walterscheid induced by topical psoralen and UVA or by a solar-simulator UV source was observed in wild-type, but not in PAF-R-deficient mice (Wolf = 6 mice. *Statistically (= 6 mice. *Statistically (= 6 mice. *Statistically (= 4 mice. *Statistically ((Walterscheid in wild-type, but not in PAF-R?/? mice (Wolf fatty acyl residue from alkyl phosphatidylcholine and PAF acetyltransferase activity that transfers an acetyl residue NCT-501 from acetyl-CoA to this newly generated lysolipid (Prescott position with arachidonoyl residues, a source of lyso-PAF and arachidonate for prostanoid and leukotriene synthesis, which as a polyunsaturated fatty acid is susceptible to non-enzymatic oxidation. Oxidation NCT-501 of esterified fatty acyl residues introduces oxy functions, rearranges bonds, and fragments carbonCcarbon bonds by -scission that generate a myriad of reaction products (Frankel, 1984). Among these are a series of phospholipids with oxidatively fragmented acyl residues that terminate with either an -oxy function or a methyl group. The latter series is usually one carbon atom shorter than the -oxy series, as expected from the -scission reaction. Among the phospholipid reaction products are those that are ligands for the PAF-R. The most potent of the non-enzymatically generated PAF analogs are native PAF as well as the butanoyl (C4-PAF) and butenoyl (C4:1-PAF) species, which are one tenth as potent as PAF (Heery em et al /em ., 1995). Previous studies from our group have used mass spectrometry to identify native PAF as well as ox-GPCs including butanoyl and butenoyl PAF species produced in response to UVB in the human epithelial cell line KB (Marathe em et al /em ., 2005). Moreover, UVB irradiation of the precursor phospholipid 1-hexadecyl-2-arachidonoyl GPC in a cell-free system generates these same products, NCT-501 consistent with a nonenzymatic process (Marathe em et al /em ., 2005). This study fits with the hypothesis that UVB, through its ability to act as a pro-oxidative stressor, generates PAF and ox-GPCs, which then Sav1 act on bone marrow-derived immunocytes to generate IL-10 through COX-2-produced prostaglandins. Compatible with this hypothesis, recent studies by Matsumura em et al /em . (2006) found that transferring lymph node cells from UV-irradiated, FITC-sensitized mice into normal recipients transferred immune tolerance. Elegant studies by this group exhibited that this cell responsible was a CD19+, B220+ B cell. These studies examining the transfer of UVB-mediated tolerance indicated that inhibition of both the serotonin and PAF-R systems were necessary to block the production of these B cells (Matsumura em et al /em ., 2006). Yet, the authors also reported previously that use of PAF-R antagonists alone were adequate to block UVB-mediated immunosuppression (Walterscheid em et al /em ., 2002), indicating differences in UVB-mediated immunosuppression and tolerance. It should be pointed out that this study does not examine which cell type or mediators induces tolerance, but instead the role of the PAF system in systemic immunosuppression. Although the PAF-R status of the CD19+, B220+ B cell implicated in tolerance has not been assessed (Matsumura em et al /em ., 2006), B cells have been described as expressing functional PAF-Rs, unlike T cells (Travers em et al /em ., 1989; Mazer em et al /em ., 1992). However, other PAF-R-positive immunocytes including monocytes and dendritic cells (Sozzani em et al /em ., 1997) could also react to skin-derived PAF agonists. Although.