Diverse functional coupling of prostanoid biosynthetic enzymes in various cell types

As also detailed in our accompanying papers in this issue, recent studies have revealed functional crosstalk and segregation between PLA2s, COXs, and terminal PG synthases in various cells (Table I). Among the PLA2s, cPLA2 is required for all three responses, and sPLA2-IIA augments the delayed response in preference to the immediate response. sPLA2-IIA associates with proteoglycans on the surface of stimulus-primed cells to exert its functions. COX-1 is utilized only in the immediate response and COX-2 is a prerequisite for the delayed response. The induced immediate response is often mediated by COX-2 rather than by COX-1, especially when the end product is PGE2. In addition to segregated utilization of these enzymes, significant crosstalk and/or synergism between them, which is often cell type specific, is also obvious. For instance, sPLA2 acts as an enhancer of COX-2 expression in rat mast cells, functional cPLA2 is required for sPLA2 induction in rat fibroblasts, and sPLA2 augments cPLA2 and COX-2 expression in mouse osteoblasts via endogenous PGE1. Moreover, differential coupling between COXs and downstream terminal PG synthases is also evident in macrophages, in which COX-1 and COX-2 are preferentially coupled with TXS and PGES, respectively. Thus, different PG-biosynthetic enzymes, acting on different cellular AA pools at different locations and being regulated by separate but interacting mechanisms, confer on the system great versatility in ensuring that both immediate and delayed AA-derived mediators are efficiently generated during cellular responses.