POSTTRANSCRIPTIONAL REGULATION OF SYNDECAN-1 EXPRESSION BY CAMP IN PERITONEAL-MACROPHAGES

Syndecan-1 is a cell surface heparan sulfate proteoglycan that is prop osed to serve in cell-cell adhesion, cell-matrix anchorage, and growth factor signaling. Its expression is temporally and spatially regulate d during epithelial-mesenchymal interactions in many developing tissue s. In some cases, this regulation appears to be achieved at the level of transcription. However, induction of syndecan-1 expression in the e mbryonic kidney mesenchyme is suggested to occur at the level of mRNA translation (Vainio, S., M. Jalkanen, M. Bernfield, and L. Saxen. 1992 . Dev. Biol. 152:221-232). To identify a system in which the regulator y mechanisms controlling syndecan-1 expression can be studied, cells o f the monocyte-macrophage lineage, which regulate the expression of ma ny cell surface receptors, were screened for syndecan-1 expression. Th e syndecan-1 gene is active in blood monocytes as well as resident and thioglycollate-elicited mouse peritoneal macrophages, but expression of the proteoglycan is regulated at two levels. First, elicited macrop hages accumulate nine-fold more syndecan-1 mRNA than do resident macro phages or circulating blood monocytes. Another member of the syndecan family of proteoglycans, syndecan-4, shows a distinct pattern of expre ssion, suggesting that this regulation is specific for syndecan-1. Sec ond, utilization of the mRNA for syndecan-1 production encounters a po st-transcriptional block in the elicited macrophages that can be overc ome by triggering agents such as E-type prostaglandins or dibutyryl cA MP, which raise intracellular cAMP levels. Dibutyryl cAMP does not ind uce syndecan-I expression in resident peritoneal macrophages, which la ck a pool of stored mRNA. This suggests that this agent promotes the p ost-transcriptional utilization of stored syndecan-1 mRNA. The induced proteoglycan appears at the cell surface as a approximately 100-kD he paran sulfate-rich isoform of syndecan-1. This suggests that a cAMP-de pendent post-transcriptional control mechanism may be present in a var iety of tissues when syndecan-1 expression is regulated.